ENDOCRINE (7%) Flashcards
DIABETES MELLITUS (DM)
Diabetes Mellitus (DM) = body has trouble moving glucose from blood into cells
==> hyperglycemia
==> starved cells
- cells need glucose as a source of energy, so cells starve despite having enough glucose in the body
INSULIN
- hormone that decreases blood glucose levels (binds to insulin receptors on surface of cells to allow glucose to enter)
- by binding to insulin receptors ==> opens glucose transporters on cell membrane to allow glucose into the cell from blood
GLUCAGON
- hormone that increases blood glucose levels
- causes liver to generate new molecules of glucose from protein / fat, and also to break down glycogen (glucose stores) when hypoglycemic
Both Insulin + Glucagon = hormones produced in the Pancreas by ISLETS OF LANGERHANS
⦁ Beta Cells (center of islets) = Insulin
⦁ Alpha cells (periphery of islets) = Glucagon
DIAGNOSIS OF DIABETES MELLITUS = occurs when blood glucose levels are too high
⦁ type I (about 10%)
⦁ type II (about 90%)
- main difference = underlying mechanism that causes hyperglycemia
TYPE I DIABETES
- Not able to produce own insulin due to autoimmune destruction of beta cells
- TYPE IV HYPERSENSITIVITY REACTION =
cell-mediated immune response - person’s own T-cells attack pancreas
- destruction of beta cells - usually occurs early on in life
- usually about 90% of beta cells are destroyed before symptoms occur
4 CLINICAL SYMPTOMS OF UNCONTROLLED DM ⦁ polyphagia (excessive eating) ⦁ polyuria (excessive urination) ⦁ polydipsia (excessive thirst) ⦁ glycosuria (glucose in urine)
PATHOPHYSIOLOGY OF SYMPTOMS
- even though there is a lot of glucose in blood, it can’t get into cells, leaving cells starved for energy
==> adipose tissue starts breaking down fat (lipolysis)
==> muscle tissue starts breaking protein
==> WEIGHT LOSS ==> leaves people feeling hungry (Polyphagia)
- High amounts of glucose in the blood –> kidneys –> some spills into urine (glycosuria)
- Body needs to get rid of excess glucose –> polyuria
- since glucose is osmotically active, water follows, and because of frequent urination = become thirsty –> polydipsia
TREATMENT
- not able to produce own insulin, but still respond to insulin
⦁ Lifelong insulin therapy
TYPE II DIABETES
D
DKA (DIABETIC KETOACIDOSIS)
- occurs more with uncontrolled type I DM, but can occur with type II DM as well
- DKA is a result of INSULIN DEFICIENCY and counterregulatory hormonal excess in diabetics as a direct response to stressful triggers: o ** INFECTION = MC ** o Infarction o Noncompliance with insulin / dosage o undiagnosed diabetes
Cortisol = hormone released with stress –> increases glucose levels
- these patients are unable to meet the demand of increased insulin requirements in response to hyperglycemia, especially during stress
DKA vs HHS
- DKA = presence of ketoacidosis
- HHS = severity of hyperglycemia
- DKA tends to occur in younger patients with type I
- HHS tends to occur in older patients with type II DM
PATHOPHYSIOLOGY
- insulin deficiency –> 1) hyperglycemia 2) dehydration 3) ketonemia (high anion gap metabolic acidosis) 4) potassium deficit (false hyperkalemia)
DKA usually occurs in type I DM but can occur in type II
1) If cells are starved for energy due to lack of glucose, Adipose tissue starts to break down fat to convert into glucose (lipolysis) –> weight loss
2) Fat is broken down into free FATTY ACIDS
3) Liver converts fatty acids into KETONE BODIES
⦁ Acetoacetic acid (keto-acid)
⦁ Beta-hydroxybutyric acid (technically not an acid, but a reduced ketone)
- These ketone bodies can be used by cells for energy, but they also increase the acidity of the blood* which can have major effects throughout the body
SYMPTOMS
⦁ Kussmaul respirations - deep / labored breathing as body tries to move CO2 out of the body to decrease acidity of blood (increase pH)
⦁ False hyperkalemia (due to H/K pump that brings more H+ ions into cells to reduce acidity of blood in exchange for K+ ions being moved out of cells into blood)
- Insulin stimulates Na / K pumps so that more K+ enters cells and more Na+ leaves cells. Without insulin, more K+ stays outside of cells ==> also leads to hyperkalemia*****
- so while there is excess K+ in the blood, the OVERALL STORES of K+ are low
⦁ High Anion Gap
- a large difference in the positive and negative ions in the serum
- largely due to buildup of ketoacids (as well as K+)
- formula = Na - (Cl + HCO3) (K not included)
- normal anion gap = 8-16
- A high anion gap value means that your blood is more acidic than normal. It may indicate that you have acidosis
DKA can occur in people who have already been diagnosed with DM and are currently on insulin
In states of stress, such as infection, body releases epinephrine –> stimulates release of glucagon –> elevates blood sugars –> hyperglycemia –> polyuria / polydipsia / glycosuria / polyphagia –> need for alternate source of energy –> fat breakdown –> ketoacidosis
⦁ Acetone - fruity smelling breath
- both ketone bodies break down into acetone
- acetone is excreted via exhalation out the lungs
- causes fruity breath
⦁ Nausea / Vomiting
⦁ Mental status changes
⦁ can cause acute cerebral edema
SIGNS / SYMPTOMS OF DKA ⦁ hyperglycemia ⦁ polyuria ⦁ polydipsia ⦁ nocturia ⦁ weakness / fatigue ⦁ confusion ⦁ N / V ⦁ may have chest pain ⦁ may have abdominal pain - more in children ⦁ mental status changes / delirium ⦁ weight loss in hx if never been diagnosed with DM I
PHYSICAL EXAM OF HHS
⦁ tachycardia
⦁ tachypnea
⦁ hypotension - if dehydrated
⦁ fever if infection was cause
⦁ decreased skin turgor (dehydration)
⦁ ** KUSSMAUL RESPIRATIONS ** - deep continuous respirations as lungs attempt to blow off excess CO2 to reduce acidosis)
⦁ ** KETOTIC BREATH ** - fruity breath with acetone
DIAGNOSIS ⦁ blood glucose level > 250 - (then start testing ketones) ⦁ ABGs or VBGs (arterial or venous blood gases) - acidic pH (low): < 7.30 = DKA o 7.25 - 7.29 = mild DKA o 7.0 - 7.24 = moderate DKA o < 7.0 = severe DKA - low bicarb levels (normal = 22-30): < 18 = DKA o 15-18 = mild DKA o 10-14 = moderate DKA o < 10 = severe DKA - shows metabolic acidosis ⦁ Ketones = positive (what distinguishes between DKA and HHS) ⦁ UA ⦁ CMP - anion gap - shows metabolic acidosis (excess H+, decreased bicarb)
** Ketone levels are what distinguishes between DKA and HHS **
TREATMENT
1) ** FLUIDS ** - for dehydration = IV NS (then see hypokalemia)
- once hypotension resolves = can be switched to 1/2 NS
- when glucose levels reach 250 = then reduce to D5 1/2 NS to prevent hypoglycemia from insulin
2) Insulin to lower blood glucose - do not over-administer insulin and cause hypoglycemia
3) Electrolytes (K+)
4) Glucose - monitor glucose level with insulin drip, make sure patient doesn’t become hypoglycemic
Lowering of the blood glucose level too fast is thought to predispose to cerebral edema
- To minimize risk of cerebral edema, lowering of the blood glucose level should be done no faster than 80mg/dl/hour
- treat any infection / stress that may have caused DKA
- monitor venous pH to make sure acidosis resolves
- monitor bicarb levels (not typically replaced, as will usually gradually improve with stabilizing)
Diabetic ketoacidosis (DKA) should always be handled in a hospitalized setting, usually an ICU, and often with an endocrinologist’s consultation, if appropriate.
HHS (HYPEROSMOLAR HYPERGLYCEMIC STATE)
- HHS is a result of INSULIN DEFICIENCY and counterregulatory hormonal excess in diabetics as a direct response to stressful triggers: o ** INFECTION = MC ** o Infarction o Noncompliance with insulin / dosage o undiagnosed diabetes
Cortisol = hormone released with stress –> increases glucose levels
- these patients are unable to meet the demand of increased insulin requirements in response to hyperglycemia, especially during stress
DKA vs HHS
- DKA = presence of ketoacidosis
- HHS = severity of hyperglycemia
- DKA tends to occur in younger patients with type I
- HHS tends to occur in older patients with type II DM
PATHOPHYSIOLOGY OF HHS
- usually occurs in type II DM with some illness that leads to REDUCED FLUID INTAKE
- ** MC = INFECTION **
1) hyperglycemia + dehydration + increased osmolarity
2) potassium deficit (false hyperkalemia)
3) absence of severe ketosis (as type II DM make enough insulin to prevent ketogenesis usually)
SIGNS / SYMPTOMS OF HHS ⦁ hyperglycemia ⦁ polyuria ⦁ polydipsia ⦁ nocturia ⦁ weakness / fatigue ⦁ confusion ⦁ N / V ⦁ may have chest pain ⦁ mental status changes / delirium
PHYSICAL EXAM OF HHS ⦁ tachycardia ⦁ tachypnea ⦁ hypotension ⦁ fever if infection was cause ⦁ decreased skin turgor (dehydration)
DIAGNOSIS
⦁ blood glucose level > 600
⦁ ABGs or VBGs (arterial or venous blood gases)
- pH > 7.30 (whereas DKA = pH < 7.30)
- low bicarb levels (normal = 22-30): > 15 = HHS
o 15-18 = mild DKA
o 10-14 = moderate DKA
o < 10 = severe DKA
(so if serum bicarb is 16+ = could be HHS or mild DKA)
- shows metabolic acidosis
⦁ Ketones = small (what distinguishes between DKA and HHS)
⦁ Serum Osmolarity** = > 320
⦁ UA
⦁ CMP - anion gap - shows metabolic acidosis (excess H+, decreased bicarb)
TREATMENT
1) ** FLUIDS ** - for dehydration = IV NS (then see hypokalemia)
- once hypotension resolves = can be switched to 1/2 NS
- when glucose levels reach 250 = then reduce to D5 1/2 NS to prevent hypoglycemia from insulin
2) Insulin to lower blood glucose - do not over-administer insulin and cause hypoglycemia
3) Potassium
- despite hyperkalemia, patient is total body potassium deficient, so correction of DKA will cause hypokalemia
- first verify renal output
⦁ 20-40 mEq/L if potassium is low / normal (K < 5.5)
⦁ if K > 5.5, hold repletion until serum K+ falls into normal range and then start repletion
4) Glucose - monitor glucose level with insulin drip, make sure patient doesn’t become hypoglycemic
5) Bicarbonate = only given in severe acidosis (pH < 7, Bicarb < 10)
- acidosis usually resolves with IV fluids + insulin
- Bicarb is associated with many complications (increased rate of cerebral edema)
Lowering of the blood glucose level too fast is thought to predispose to cerebral edema
- To minimize risk of cerebral edema, lowering of the blood glucose level should be done no faster than 80mg/dl/hour
- treat any infection / stress that may have caused HHS - monitor venous pH to make sure acidosis resolves
- monitor bicarb levels (not typically replaced, as will usually gradually improve with stabilizing)
HHS should always be handled in a hospitalized setting, usually an ICU, and often with an endocrinologist’s consultation, if appropriate.
GYNECOMASTIA
Gynecomastia = benign enlargement of the breast in males - due to increased effective estrogen
- caused by either increased production or decreased degradation of estrogen, or due to decreased androgens
Gynecomastia = enlargement of the breast tissue itself, which consists of glands.
Pseudogynecomastia = the appearance of enlarged breasts in overweight men. However, this enlargement is because of an increase in fat tissue around the breasts, not enlargement of gland tissue in the breast
SEEN IN 3 MAIN GROUPS
⦁ Infants - due to high maternal estrogen
⦁ Puberty - especially 10-14 y/o - may last 6 months - 2 years
⦁ Older Males - due to decreased androgen production
Gynecomastia sometimes occurs during infancy and puberty. The enlargement is usually normal and transient in puberty, lasting a few months to a few years. Breast enlargement also commonly takes place after age 50.
During infancy and puberty, bilateral, symmetric, smooth, firm, and tender enlargement of breast tissue under the areola is normal
In infants and boys, the MC cause is
⦁ Physiologic gynecomastia
In men, the most common causes are
⦁ Persistent pubertal gynecomastia
⦁ Idiopathic gynecomastia
⦁ Drugs (particularly spironolactone, anabolic steroids, and antiandrogens)
CAUSES
⦁ Idiopathic
⦁ Persistent pubertal gynecomastia
⦁ Medications:
- Spironolactone***
- Ketoconazole
- Cimetidine
- 5-alpha reductase inhibitors (finasteride / dutasteride)
- Digitalis / Digoxin
- GnRH agonists (Leuprolide)
- Omeprazole
- Haldol
⦁ Others:
- Cirrhosis***
- Testicular tumors (choriocarcinomas)
- Hyperthyroidism
- Chronic renal disease
- Klinefelter syndrome
- Alcoholism***
PATHOPHYSIOLOGY
- The hormone estrogen is responsible for the growth of glandular tissue, as well as the suppression of testosterone secretion. Estrogen suppresses LH, the hormone that is responsible for testicular secretion of testosterone. This process of hormonal imbalance leads to gynecomastia.
SYMPTOMS ⦁ palpable mass of tissue > 0.5 cm - centrally located (usually underlying the nipple) ⦁ symmetrical ⦁ classically bilateral ⦁ often tender to palpation
DIAGNOSIS
⦁ clinical
⦁ check testosterone levels
⦁ mammogram if breast cancer suspected
The workup of gynecomastia should include a chest radiograph, β-human chorionic gonadotropin determination, LH, FSH, estrogen and testosterone levels, LFTs, prolactin, and thyroid function tests.
Typically, the estrogen:testosterone ratio is high
If hcg is elevated, then a testicular ultrasound should be performed to look for testicular tumor.
Additionally, if the testes are small, a karyotype should be obtained to look for Klinefelter’s syndrome
Patients with hypogonadism, impotence, or galactorrhea may have abnormal prolactin levels associated with prolactinomas
Patients with physiologic or idiopathic gynecomastia are evaluated again in 6 mo
TREATMENT
- depends on cause
- stop offending medication
- observation if early in disease course ==> most regress spontaneously
- Ideal treatment should start within first 6 months, as after 12 months, tissue may undergo fibrosis
o Medication management
⦁ SERM (selective estrogen modulators) - Tamoxifen
⦁ Aromatase inhibitors - block estrogen synthesis
⦁ Androgens
o Surgery - if medications fail, if large breasts, if cosmetically unappealing, if fibrosis, etc.
Patient will present as → 54-year-old male on chronic a potassium-sparing diuretic with bilateral breast tissue swelling and tenderness (due to spiro!)
Patient will present as → a 14-year-old boy who notices a lump under the nipple of his left chest. He reports mild pain when touched. There is no breast discharge or changes in the skin. On physical examination, pubic hair is Tanner stage IV and has a testicular volume of 9 mL bilaterally. Palpation of the left chest shows a 3.5 cm mass beneath the nipple
GALACTORRHEA
Milky breast secretions in a non-lactating person
MC CAUSE = PITUITARY ADENOMA - PROLACTINOMA
Most tumors in women are microadenomas (< 10 mm in diameter), but a small percentage are macroadenomas (> 10 mm) when diagnosed
OTHER CAUSES ⦁ Medications - antipsychotics - cimetidine - TCAs - OCPs - Depo Provera
⦁ Pituitary adenoma
⦁ Hypothyroidism
SYMPTOMS
⦁ galactorrhea
DIAGNOSIS
⦁ Prolactin levels (levels > 200 = prolactin-secreting pituitary adenoma)
⦁ T4 / TSH - rule out hypothyroidism
⦁ CT or MRI = method of choice for adenomas
TREATMENT ⦁ **** dopamine agonist **** = Cabergoline or Bromocriptine - SE = orthostatic hypotension - Cabergoline associated with less SE
Patient will present as → a 26-year-old non-lactating woman with a 3-month history of bilateral milky breast secretions and amenorrhea. Her serum HCG is negative and her serum prolactin is elevated at 220
HYPERPROLACTINEMIA
= elevated prolactin levels in the blood
Pituitary gland = made up of anterior + posterior pituitary, each have cells that release certain hormones
LACTOTROPH CELLS = in anterior pituitary - secrete prolactin hormone
PATHOPHYSIOLOGY
o In men: prolactin decreases testosterone production
(elevated prolactin inhibits GnRH –> decreased FSH / LH –> decreased testosterone)
o In women:
- during pregnancy, increased estrogen stimulates increased production of prolactin –> stimulate alveolar cells in the breast to divide / enlarge in preparation for breast-feeding once baby is born
- stops ovulation / menstruation = Amenorrhea
Elevated Prolactin inhibits GnRH release from hypothalamus ==> decreased FSH / LH ==> decreased estrogen levels
= why women typically don’t have a period while breastfeeding
Prolactin levels are kept in check via 2 ways
1) Hypothalamus secretes Dopamine (Prolactin inhibiting factor)
- dopamine binds to specific receptors on lactotrophs to inhibit release of prolactin
2) Hypothalamus secretes Thyrotropin Releasing Hormone ==> stimulates Prolactin release
If prolactin levels rise for any reason ==> signals more dopamine to be released from hypothalamus (negative feedback)
CAUSES OF HYPERPROLACTINEMIA
⦁ Physiologic Hyperprolactinemia
- Pregnancy / Lactation
- levels of prolactin typically return back to normal after
⦁ Prolactinoma = ** MC Pathologic cause **
- pituitary adenoma = benign tumor of lactotroph cells -> grow out of control- release excess amts of prolactin
⦁ Hypothyroidism
- in effort to increase thyroid hormone levels, hypothalamus increases levels of thyrotropin releasing hormone (TRH), which in turn also increases prolactin
⦁ Medications - Dopamine antagonists (block dopamine) ==> blocks inhibition of prolactin cells => hyperprolactinemia o metoclopramide o promethazine o prochlorperazine o antipsychotics
- Estrogens - directly stimulate lactotrophs
- SSRIs / TCAs / Cimetidine / Verapamil (CCB)
⦁ Damage to hypothalamic-pituitary stalk due to
- trauma
- nearby brain tumors
- brain surgery
SYMPTOMS OF HYPERPROLACTINEMIA
o Women
⦁ Galactorrhea
⦁ Amenorrhea / Anovulation (inhibits FSH / LH)
o Men
⦁ Gynecomastia
⦁ Erectile dysfunction (inhibits FSH / LH -> inhibits testosterone)
o Others
⦁ Headaches / Impaired vision
- Pituitary Adenoma can compress optic chiasm –> Bitemporal Hemianopsia
- brain “mass effect”
In postmenopausal women, hyperprolactinemia most commonly causes manifestations of brain mass effect.
Before diagnosing hyperprolactinemia in a young woman, it’s important to rule out pregnancy.
Hyperprolactinemia is a pituitary disorder that can present with amenorrhea, galactorrhea, decreased libido, and infertility.
DIAGNOSIS
⦁ elevated prolactin levels = best initial test!
- normal prolactin levels = up to 20
- hyperprolactinemia levels = > 200!
⦁ pregnancy test (to test for physiologic causes)
⦁ brain MRI to check for pituitary adenomas
TREATMENT
- depends on underlying cause
⦁ ** Dopamine Agonists **
- stimulate dopamine receptors ==> increased dopamine, which will then inhibit prolactin levels
o ** Cabergoline **
o ** Bromocriptine **
- SE = orthostatic hypotension
- Cabergoline = 1st line, less SE
⦁ Surgery if prolactinoma
- If there is a residual tumor tissue after the surgical excision of prolactinoma, it should be managed through irradiation.
⦁ If hypothyroidism = give replacement thyroid hormone
