ABIM 2015 - Endocrine Flashcards
Calcineurin Inhibitors (CYCLOSPORINE and TACROLIMUS) - by “inhibiting secretion of”; HIV Protease Inhibitors (-“NAVIR”) and Atypical Antipsychotics (CLOzapine, OLANzapine) - by “resistance to” (and causing WEIGHT GAIN) can cause DRUG-INDUCED DM?
Inhibit secretion of and cause resistance to INSULIN
MACROvascular (coronary, cerebral, peripheral) and MICROvascular (RETINOpathy, NEPHROpathy, NEUROpathy) disease is seen in this endocrinological disorder?
Diabetes Mellitus (DM)
When the body becomes RESISTANT to the effects of INSULIN, the PANCREAS SECRETES MORE INSULIN as well as another compound that can be tested for in order to CHECK that the ELEVATED INSULIN in the BLOOD is ENDOGENOUS (made by the pancreas and not exogenously-administered)?
C-peptide (EACH insulin MOLECULE secreted by the pancreas has ONE C-peptide attached to it)
Cystic Fibrosis, Hemochromatosis, Acromegaly, Cushing Syndrome, Glucagonoma, Pheochromocytoma, HYPERthyroidism, Down/Klinefelter/Turner/Wolfram/Prader-Willi/Stiff-Man (SYNDROMES), Myotonic Dystrophy, THIAZIDES (Chlorthalidone, HCTZ) and NIACIN (vit B3) can all cause this endocrinological disorder?
Diabetes Mellitus (DM)
What lab TEST is helpful in the DIAGNOSIS of HYPOglycemia in patients WITHOUT DM?
C-peptide (because EACH insulin MOLECULE secreted by the pancreas has ONE C-peptide attached to it)
What patients should be tested for PANCREATIC AUTO-Ab’s (islet-cell Ab’s or glutamic acid decarboxylase Ab’s) in order to differentiate between TYPE 1 DM and TYPE 2 DM?
OBESE patients (because they have BOTH increased levels of insulin and therefore C-peptide in the BLOOD)
Why is it important to determine WHICH TYPE (1 or 2) DM a patient has?
Because TYPE 1 DM which is IMMUNE MEDIATED (PANCREATIC AUTO-Ab’s: islet-cell Ab’s or glutamic acid decarboxylase Ab’s) should be TREATED with INSULIN AS SOON AS POSSIBLE to AVOID DKA (high MORBIDITY and MORTALITY)
What ASYMPTOMATIC patients should be SCREENED for DM?
ALL those who have a SUSTAINED BP of 135/80 mmHg (treated or untreated)
An ABNORMAL Oral Glucose Tolerance Test on TWO (2) separate occasions, a SINGLE RANDOM PLASMA GLUCOSE ≥200 mg/dL WITH SYMPTOMS (polyuria, polydipsia, blurred vision) are ALL diagnostic for what?
Diabetes Mellitus (DM)
This TYPE of DM presents DRAMATICALLY with SEVERE SYMPTOMS of hypoglycemia (fatigue, polyuria, polydipsia, polyphagia, visual blurring, N/V and dehydration) and is caused by slow AUTOIMMUNE destruction of insulin-producing pancreatic β-cells by Ab’s in patients with HLA - DQA/DQB susceptibility in CHROMOSOME 6?
TYPE 1 DM (HIGH RISK for DKA if not diagnosed and treated right away with INSULIN which results in HIGH MORBIDITY and MORTALITY)
Why must INSULIN therapy be STARTED RIGHT AWAY in a patient diagnosed with TYPE 1 DM?
Because once SYMPTOMATIC, a patient with TYPE 1 DM has approximately 80% pancreatic β-cells destroyed and has a HIGH RISK for DKA if not treated right away with INSULIN which results in HIGH MORBIDITY and MORTALITY
Why does the need for INSULIN dose REDUCTION (NOT D/C) occur once a patient with TYPE 1 DM is diagnosed and treated with INSULIN?
Because the RESIDUAL function of the REMAINING β-cells IMPROVES and can remain that way for MONTHS to YEARS (precisely why insulin dose should be LOWERED NOT D/C’d)
When can a patient who INITIALLY presents with DKA and is treated with INSULIN and IVF’s, have their INSULIN DISCONTINUED and treated with LIFESTYLE changes and ORAL hypoglycemic agents?
When they do NOT HAVE TYPE 1 DM (absence of pancreatic auto-Ab’s or the characteristic HLA-gene associations
Classic HYPOglycemic symptoms (polyuria, polydipsia, blurred vision) + RANDOM GLUCOSE >200 mg/dL?
DIAGNOSTIC FOR: Diabetes Mellitus (DM)
FASTING PLASMA GLUCOSE ≥126 mg/dL on TWO SEPARATE OCCASIONS on TWO DIFFERENT DAYS?
DIAGNOSTIC FOR: Diabetes Mellitus (DM)
A PLASMA GLUCOSE of ≥200 mg/dL WHILE performing an ORAL 2-HOUR 75 g GLUCOSE TOLERANCE TEST on TWO SEPARATE OCCASIONS on TWO DIFFERENT DAYS?
DIAGNOSTIC FOR: Diabetes Mellitus (DM)
A RANDOM PLASMA GLUCOSE ≥200 mg/dL DIAGNOSTIC FOR: Diabetes Mellitus (DM)
DIAGNOSTIC FOR: Diabetes Mellitus (DM)
A HbA1c ≥6.5% on TWO SEPARATE OCCASIONS on TWO DIFFERENT DAYS?
DIAGNOSTIC FOR: Diabetes Mellitus (DM)
When DM is due to a SLOW DECLINE (decades) in β-cell FUNCTION that is NOT IMMUNE-MEDIATED (not due to pancreatic auto-Ab destruction of the β-cells) resulting in DECREASED INSULIN SECRETION over DECADES AND DEVELOPMENT of RESISTANCE to the effects of INSULIN, what TYPE of DM is it?
TYPE 2 DM
Which patient is more likely to develop DM, one with a FAMILY H/O TYPE 1 DM or one with a FAMILY H/O TYPE 2 DM?
TYPE 2 DM by FAR (much stronger genetic association and inheritance)
Why although DKA can occur in TYPE 2 DM it is VERY RARE?
Because the pancreatic insulin-producing β-cells are NOT immunologically DESTROYED as they are in TYPE 1 DM and the DECLINE in FUNCTION is SLOW with some remaining β-cells that continue to function and not result in the LIPOLYSIS seen in complete or severe INSULIN DEFICIENCY thus not creating a KETO-ACID emergency
CENTRAL OBESITY + HTN + HYPERlipidemia + DM = ?
The Metabolic Syndrome
Diet & Exercise, Metformin, Lipase Inhibitors (orlistat), α-glucosidase inhibitors (acarbose, voglibose -“bose”), Thiazolidinediones (-“glitazones”) and possibly Bariatric Surgery (BMI >40) have all SHOWN what DEFINITIVE CHANGE that other measures/drugs have NOT?
These ALL SUCCESSFULLY PREVENT or DELAY the onset of TYPE 2 DM by UP TO 3 YEARS
After SCREENING for DM at the FIRST OBSTETRIC VISIT using the usual criteria, when SHOULD ALL PREGNANT women be SCREENED for GESTATIONAL DM and with WHAT TEST?
At 24-28 WEEKS gestation AFTER an 8-HOUR FAST with the ORAL 2-HOUR 75 g GLUCOSE TOLERANCE TEST
What results on the ORAL 2-HOUR 75 g GLUCOSE TOLERANCE TEST are considered POSITIVE for GESTATIONAL DIABETES (NOT DM)?
FASTING: ≥92 mg/dL
1-HOUR: ≥180 mg/dL
2-HOUR: ≥153 mg/dL
What is considered a NORMAL FASTING PLASMA GLUCOSE?
Normal FASTING Plasma Glucose
What is CONSIDERED a NORMAL RANDOM PLASMA GLUCOSE?
Normal RANDOM Plasma Glucose
What is CONSIDERED a NORMAL HbA1c?
Normal HbA1c
Physiologically, during pregnancy, there is a NORMAL INCREASED INSULIN RESISTANCE and when a PREGNANT woman’s pancreas CANNOT increase insulin SECRETION enough to overcome the resistance, this results in what condition?
GESTATIONAL DIABETES
When this condition is NOT treated in the PREGNANT woman, there is a HIGH risk for fetal MACROSOMIA (large baby >4,500 g), PREMATURE delivery, PREECLAMPSIA, STILLBIRTH, C-SECTION, JAUNDICE, HYPOglycemia/HYPOcalcemia and fetal RESPIRATORY COMPROMISE?
GESTATIONAL DIABETES
When can PREGNANT women be EXCLUDED from testing for GESTATIONAL DIABETES and when SHOULD it be done EARLIER than 24-28 WEEKS gestation?
EXCLUDED: 30, previous H/O gestational diabetes or Polycystic Ovarian Syndrome - “PCOS”, previous fetus with MACROSOMIA (large baby >4,500 g), FAMILY H/O DM, or NON-WHITE
How is GESTATIONAL DIABETES treated?
LIFESTYLE MODIFICATIONS (diet and exercise), INSULIN (if these changes are not sufficient) or ORAL agents (METFORMIN and GLYBURIDE if INSULIN is refused)
METFORMIN, GLYBURIDE, INSULIN are SAFE to use in?
PREGNANT WOMEN (gestational diabetes or otherwise)
Gestational Diabetes and TYPE 2 DM are VERY likely to OCCUR in whom?
In women who have been DIAGNOSED with GESTATIONAL DIABETES in a previous pregnancy
What is the CHILD of a mother with PRE-PREGNANCY OBESITY who developed GESTATIONAL DIABETES at RISK for?
CHILDHOOD OBESITY
Why can conditions such a ACROMEGALY, CUSHING SYNDROME and GLUCAGONOMA) lead to DIABETES?
Because their HORMONAL ACTIONS are ANTAGONISTIC to INSULIN
What ORAL medications SIGNIFICANTLY INCREASE the RISK of HYPOglycemia making PROPER self-monitoring by the patient CRUCIAL?
SULFONYLUREAS
What is the most COMMON cause of the VARIABILITY in DAY-to-DAY blood GLUCOSE LEVELS?
DIET and EXERCISE
RBC’s live for 120 days, in states of SUSTAINED HYPERglycemia, GLUCOSE attaches to Hb by a process called GLYCOSYLATION and therefore, the average BLOOD GLUCOSE level during the 3 MONTHS can be tested for by?
HbA1c (measuring the glycosylated Hb)
When should the HbA1c be tested for?
Every 3 MONTHS if patient’s therapy is being adjusted and every 6 MONTHS if on STABLE therapy
What routine test used for DIABETICS should NOT be done in patients that receive DIALYSIS, have HEMOLYTIC ANEMIA or have had a RECENT BLOOD TRANSFUSION?
HbA1c, because it will be FALSELY lowered due to the presence of ERYTHROCYTES that are not 120 days old
What should be the HbA1c GOAL for NON-PREGNANT patients with a LONG LIFE EXPECTANCY, NO CARDIOVASCULAR DISEASE and a SHORT DURATION of DM?
HbA1c
What should be the HbA1c GOAL for patients with a LONG-DURATION of DM, CARDIOVASCULAR DISEASE, MULTIPLE CO-MORBIDITIES or H/O SEVERE HYPOglycemia?
HbA1c
What is the AVERAGE DAILY BLOOD GLUCOSE in a patient with a HbA1c of 7.0, 8.0?
Average daily blood glucose in HbA1c of 7.0 - 154 mg/dL
Average daily blood glucose in HbA1c of 8.0 - 183 mg/dL
What is the MAJOR CARDIOVASCULAR RISK FACTOR for a patient with DM?
ATHEROSCLEROSIS (due to inflammatory state of DM)
Should ASPIRIN be used in ALL patients with DM to decrease CARDIOVASCULAR RISK if there are no CONTRAINDICATIONS?
YES!!
What is the RECOMMENDED EXERCISE DURATION and INTENSITY for DIABETICS for the PREVENTION of CARDIOVASCULAR RISK?
MODERATE EXERCISE for at LEAST 150 min/WEEK
EVEN with NORMAL CHOLESTEROL LEVELS, in ALL patients >40 with DM and at least ONE other cardiovascular risk factor (AGE >65, smoking, obese, HTN) what MEDICATIONS MUST be RECOMMENDED as they have SIGNIFICANT BENEFITS?
STATINS
What is the FIRST RECOMMENDATION for ALL patients diagnosed with DM?
LIFESTYLE MODIFICATIONS (diet, exercise, weight loss)
What happens to BLOOD GLUCOSE levels when a patient with DM EXERCISES when their INSULIN LEVELS are LOW (early, before breakfast)?
They RISE!! because exercise INDUCES hepatic gluconeogenesis and no insulin was taken (as patient did not eat breakfast yet)
What PROCEDURE performed in patients with MORBID OBESITY and DM can cause DM to go into remission?
BARIATRIC surgery (BMI >40)
Why do MOST patients with TYPE 2 DM eventually require MORE than ONE drug to PROPERLY maintain their blood glucose?
Because in TYPE 2 DM, the LOSS of pancreatic β-cell function is PROGRESSIVE in ADDITION to underlying INSULIN RESISTANCE
What should be RECOMMENDED for ALL patients AT TIME OF DIAGNOSIS of DM?
LIFESTYLE MODIFICATIONS (diet, exercise, weight loss) AND START a NON-INSULIN agent (METFORMIN)
What are the MAIN DRUG options for BLOOD GLUCOSE CONTROL?
- ORAL for control of POST-PRANDIAL BLOOD GLUCOSE [sulfonylureas (glipizide, -“ride, mide, zide”), α-glucosidase inhibitors (acarbose, voglibose -“bose”), meglitinides (rapaglinide, -“glinide”) and dipeptidyl peptidase-4 inhibitors (sitagliptin, -“gliptin”)
- INJECTABLE that SLOW GASTRIC EMPTYING and SUPPRESS GLUCAGON (by the pancreas) - pramlintide, exenatide, liraglutide -“tide”
- INSULIN
What is the BEST ORAL agent to INITIALLY ADD to LIFESTYLE MODIFICATIONS (diet, exercise, weight loss) for MOST patients diagnosed with DM?
METFORMIN
What DM DRUGS should be AVOIDED in OLDER patients and those with IMPAIRED KIDNEY FUNCTION?
SULFONYLUREAS (glybuRIDE, chlorpropaMIDE) as these two in particular, have LONG HALF-LIVES and can cause PROFOUND HYPOglycemia (DEADLY) as well as their association with MYOCARDIAL DAMAGE (MI)
Besides these TWO (2) third-generation SULFONYLUREAS, other sulfonylureas have been associated with MYOCARDIAL DAMAGE (MI) and should be AVOIDED
gliclaZIDE and glimepiRIDE
gliclaZIDE and glimepiRIDE?
Third-generation SULFONYLUREAS NOT associated with myocardial damage (MI) as the act EXCLUSIVELY on pancreatic β-cells (not also on myocardial cells)
What should be done next for treating DM in a patient in whom LIFESTYLE MODIFICATIONS and ORAL agents either DON’T or are NO LONGER sufficient in controlling their BLOOD GLUCOSE levels?
ADD INSULIN (ie NPH insulin at BEDTIME + DAYTIME METFORMIN)
What are NPH insulin, insulin DETEMIR and insuline GLARGINE?
LONG-ACTING forms of insulin
When should a long-acting form of INSULIN (NPH insulin) be used for controlling BLOOD GLUCOSE in DM?
At BEDTIME or FIRST THING in the MORNING
In order to MINIMIZE and PREVENT unpredictable episodes of HYPOglycemia DUE TO the DAY-to-DAY VARIABILITY of INSULIN ABSORPTION (diet, exercise, etc.), what INSULIN preparations work BEST?
BASAL + PRE-PRANDIAL INSULINS (same as used in TYPE 1 DM)
Why do patients with TYPE 1 DM require LESS INSULIN than those with TYPE 2 DM?
Because patients with TYPE 1 DM are VERY SENSITIVE to INSULIN and those with TYPE 2 DM have a variable RESISTANCE to insulin
What is the average DIALY requirement of INSULIN for MOST patients where the LOWER limit is the requirement for patients with TYPE 1 DM and the HIGHER limit, the requirement for those with TYPE 2 DM?
0.5 - 1.5 units/kg/day
How is a BASAL (NPH insulin) and a PRANDIAL INSULIN given?
1/2 of the DAILY dose is given as the BASAL (NPH insulin) INSULIN and the remainder of the DAILY dose is given in THREE (3) injections BEFORE EACH MEAL (ideally, these 3 injections would be approximated to the meal’s carbohydrate content ie 1 unit for every 10-15 g of carbs and 1 unit for every 25 mg/dL the PRE-PRANDIAL glucose level was above 100 mg/dL for TYPE 2 DM and for every 50 mg/dL over 100 mg/dL in TYPE 1 DM)
Why are ONCE-TWICE DAILY, SOLO REGIMENS with INTERMEDIATE-ACTING INSULINS (NPH insulin) or PRE-MIXED INSULINS (70%/30% preparations, etc.) NOT OPTIMAL even though they are less costly and more convenient?
Because they can cause more FREQUENT and UNPREDICTABLE HYPOglycemia and WEIGHT GAIN
This compound works by DECREASING HEPATIC GLUCOSE production, INCREASES PERIPHERAL GUCOSE UPTAKE and supports ANABOLISM (building cells?)
INSULIN
These compounds work by STIMULATING INSULIN SECRETION from PANCREATIC β-cells but MOST (earlier 1st and 2nd generation) have been linked to MYOCARDIAL DAMAGE and CANNOT be used in OLDER patients or those with RENAL dysfunction?
SULFONYLUREAS (only gliclaZIDE and glimepiRIDE are safe to use)
This compound works by DECREASING HEPATIC GLUCOSE production, DECREASES FREE FATTY ACIDS and INCREASES insulin-mediated UPTAKE of GLUCOSE in MUSCLES (can cause lactic acidosis in those with RENAL/LIVER dysfunction and in those with EtOH abuse)?
METFORMIN (Biguanide)
These compounds work by INHIBITING POLYSACCHARIDE ABSORPTION (carbohydrates)?
α-glucosidase inhibitors (acarbose, voglibose -“bose”)
These compounds work by activating receptors that regulate gene expression, increase PERIPHERAL UPTAKE of GLUCOSE and DECREASE HEPATIC GLUCOSE production?
THIAZOLIDINEDIONES (-“glitazones”) - these cause HF, MI, macular edema, osteoporosis and bladder cancer - DO NOT USE
This medication used in treatment of DM, has been LINKED to BLADDER CANCER, HF, MI and MORTALITY?
rosiGLITAZONE (“not so rosy” - THIAZOLIDINEDIONES)
These compounds work by STIMULATING INSULIN SECRETION from PANCREATIC β-cells (same effect as sulfonylureas) but have NOT been show to cause the ADVERSE EFFECTS of sulfonylureas?
MEGLITINIDES (rapaGLINIDE, nateGLINIDE)
What is the DIFFERENCE between the MEGLITINIDES (rapaGLINIDE, nateGLINIDE) and the SULFONYLUREAS (glipizide, -“ride, mide, zide”) in their mechanism of action and SAFETY?
BOTH have the SAME mechanism of action (STIMULATING INSULIN SECRETION from PANCREATIC β-cells) HOWEVER, of the sulfonylureas, ONLY gliclaZIDE and glimepiRIDE are safe to use as the rest cause MYOCARDIAL DAMAGE and PROFOUND HYPOglycemia in OLDER patients and those with RENAL dysfunction
This compound works by INHIBITING FAT ABSORPTION?
ORLISTAT (Lipase Inhibitor)
These DRUGS used in treating DM, pramlinTIDE, exenaTIDE, liragluTIDE AND sitaGLIPTIN, saxaGLIPTIN, vildaGLIPTIN (-“tide, -gliptin”) work in which way?
SLOW GASTRIC EMPTYING and SUPPRESS GLUCAGON SECRETION by the pancreas (can cause pancreatitis, N/V and rashes)
What TYPE of INSULIN agents are LISPRO, ASPART, GLULISINE and how quickly do they act?
RAPID-ACTING INSULINS (onset 5-15 min, peaks 45-90 min lasts 2-4 hrs)
Which are the RAPID-ACTING INSULINS (5-15 min, peak 45-90 min last 2-4 hrs)?
LISPRO, ASPART, GLULISINE
What quickly does REGULAR INSULIN act?
SHORT-ACTING (not rapid) - (onset 30 min-1 hr, peaks 2-4 hrs, lasts 4-8 hrs)
What TYPE of INSULIN is NPH insulin and how quickly does it act?
BASAL (long-acting) - (onset 1-3 hrs, peaks 4-10 hrs, lasts 10-18 hrs) - so if you take it first thing in the morning, it will be ready for LUNCH and if you take it at bedtime, it will be ready for BREAKFAST
What is the ONLY difference between the BASAL (long-acting) insulins DETEMIR or GLARGINE and NPH insulin?
DETEMIR and GLARGINE have NO PEAKS (steady blood levels)
ALL patients (previously DIAGNOSED with DM or NOT) ADMITTED to the hospital should be tested with these TWO (2) labs for assessment of their glucose status?
PLASMA GLUCOSE and HbA1c (plasma glucose should be taken frequently ie BEFORE MEALS and BEDTIME or EVERY 6 HOURS if NPO)
What should be done for a patient with DM admitted to the hospital who had been taking ONLY PO MEDS to control their BLOOD GLUCOSE and is now made NPO?
D/C PO agents
May continue the PO agents IF patients ARE EATING PO EXCEPT SULFONYLUREAS (glipizide, -“ride, mide, zide”) and MEGLITINIDES (rapaglinide, -“glinide”) as these can cause HYPOglycemia if PO food intake is unpredictable or stopped
In the SETTING of LACTIC ACIDOSIS, use of IMAGING with CONTRAST DYE, or LIVER DISEASE (acute or chronic) this MEDICATION MUST BE STOPPED as it can cause LACTIC ACIDOSIS if continued?
METFORMIN (Biguanide)
In patients with DM admitted to the hospital, these agents MUST BE STOPPED if the patient has ANY suspected HEART DISEASE, EDEMA, LIVER DISEASE (acute or chronic) or OSTEOPOROSIS?
THIAZOLIDINEDIONES (-“glitazones”)
What should the BLOOD GLUCOSE GOAL be for CRITICALLY ILL patients and how should it be most OPTIMALLY controlled?
140-180 mg/dL with IV INSULIN (for all other patients NO LOWER than 90 and NO HIGHER than 180 mg/dL when taken RANDOMLY post-prandially with 140 mg/dL fasting and pre-prandially )
What is REQUIRED for hospitalized patients treated with INSULIN if a SLIDING-SCALE is to be used?
BASAL INSULIN (due to the potential wide swings in blood glucose)
BEST approach to treating hospitalized patients requiring INSUIN is the SAME as outpatients requiring INSULIN which is done in what way?
Give 1/2 of the DAILY dose as the BASAL (NPH insulin) INSULIN and give the remainder of the DAILY dose in THREE (3) injections BEFORE EACH MEAL (ideally, these 3 injections would be approximated to the meal’s carbohydrate content ie 1 unit for every 10-15 g of carbs and 1 unit for every 25 mg/dL the PRE-PRANDIAL glucose level was above 100 mg/dL for TYPE 2 DM and for every 50 mg/dL over 100 mg/dL in TYPE 1 DM)
HYPERglycemic HYPERosmolar Syndrome (HHS) and DKA can occur in what states?
INSULIN-DEFICIENCY (induces hepatic gluconeogenesis worsening HYPERglycemia as well as the HYPERglycemia that occurs from dietary GLUCOSE in the absence of INSULIN)
What are the THREE (3) most COMMON cause of DKA?
New-Onset TYPE 1 DM, UNDER-DOSING of INSULIN and MISSED INSULIN DOSING (alone or in the setting of infection or serious illness)
A patient with TYPE 1 DM with COMPLETE INSULIN DEFICIENCY will develop DKA (HCO3¯
BLOOD GLUCOSE: ~400-500 mg/mL
A patient with DM who is NOT EATING/DRINKING or a patient with DM and LIVER DISEASE or EtOH-associated HEPATIC IMPAIRMENT with a resulting DECREASED HEPATIC GLUCOSE PRODUCTION (gluconeogenesis from hepatic glycogen stores) will develop DKA (HCO3¯
BLOOD GLUCOSE: ~200-250 mg/mL (because the liver gets slowly depleted of glycogen stores (pt who isn’t eating) used for gluconeogenesis and glucose rises slowly until the liver is depleted or the process of gluconeogenesis is hampered (by the injured liver) and fatty acid breakdown and ketogenesis occur because glucose is still not available to the cells/organs that require it in the continued absence of insulin - which stops lipolysis)
What is the PRIMARY cause of HYPERglycemia in DKA?
INDUCED HEPATIC GLUCONEOGENESIS (glucose production by the liver from glycogen stores) due to the ABSENCE of INSULIN
An OLDER patient with ONLY a PARTIAL INSULIN DEFICIENCY (TYPE 2 DM) can develop HYPERglycemia and DEHYDRATION SLOWLY over days to weeks and if they still PRODUCE just ENOUGH INSULIN to PREVENT LIPOLYSIS (thus no ketoacidosis) but NOT ENOUGH to control the BLOOD GLUCOSE LEVEL, they will remain NON-KETOTIC and IF they DRINK SUGARY LIQUIDS to quench their THIRST or EAT SUGARY FOODS and if that patient has an IMPAIRED KIDNEY EXCRETION of GLUCOSE or a CO-EXISTING INFECTION or ILLNESS what can develop and with what BLOOD GLUCOSE LEVEL?
HYPERglycemic HYPERosmolar Syndrome (HHS) - a SEVERE HYPERosmolar NON-KETOTIC HYPERglycemia with VERY HIGH GLUCOSE LEVELS (>700 mg/dL) and NORMAL SERUM HCO3¯ (24 meq/L)
POLYuria, POLYdipsia, Weight Loss are the EARLY SYMPTOMS of what DIABETIC situation?
HYPERglycemia
AMS, LETHARGY, DROWSINESS, FOCAL NEUROLOGIC DEFICITS, N/V, ABD PAIN, HYPERventilation and COMA are the LATE SYMPTOMS of what DIABETIC situation?
HYPERglycemia
What MUST be done AT THE SAME TIME of INSULIN administration in a patient with DKA and why?
POTASSIUM (K⁺) administration, because ALTHOUGH SERUM K⁺ levels “appear” normal, they do so because INTERcellular K leaked out into the serum and INSULIN administration RAPIDLY moves the K⁺ BACK INTO THE CELLS resulting in severe HYPOkalemia (decreased SERUM K⁺)
Besides blood work performed in assessing and treating a patient with DKA (glucose, electrolytes, Cr, BUN, CBC, U/A, Plasma Osmolality, Serum Ketones and an ABG, what OTHER test should be done due to the SIGNIFICANT risk of SEVERE ELECTROLYTE DISTURBANCES?
ECG
How often should SERUM GLUCOSE and ELECTROLYTES be checked when treating DKA?
SERUM GLUCOSE: HOURLY
ELECTROLYTES: every 2-4 HOURS
Where should patients with DKA or HYPERglycemic HYPERosmolar Syndrome (HHS) be treated?
ICU
Due to KETOACIDOSIS ALONE, EVEN in the ABSENCE of an INFECTION, how HIGH can the WBC count be in DKA?
> 20,000!!!!!
Do patients with DKA mount a FEVER if an INFECTION is concomitantly present?
USUALLY NOT (so absence of a fever, does NOT r/o infection)
When will a patient with DKA have DKA-ASSOCIATED ABDOMINAL PAIN that if seen WITHOUT this co-existing condition is likely attributed to ANOTHER intra-abdominal process?
When SERUM HCO3¯
What BLOOD test is SIGNIFICANTLY ELEVATED in patients with DKA that IS NOT a reliable indicator for PANCREATITIS in this SETTING?
AMYLASE (can be >1000 units/L)
What BLOOD GLUCOSE level is considered HYPOglycemic resulting in the BRAIN-MEDIATED ACTIVATION of the PANCREAS, LIVER and ADRENAL GLANDS to RAISE the BLOOD GLUCOSE LEVEL?
BLOOD GLUCOSE
DKA and HYPERglycemic HYPERosmolar Syndrome (HHS) are known as what CRISES?
HYPERglycemic CRISES
When treating HYPERglycemic CRISES DKA and HYPERglycemic HYPERosmolar Syndrome (HHS) with IVF’s using NS (while monitoring serum Na levels every 2-4 hours) and giving INSULIN and K⁺, what do you CHANGE when the BLOOD GLUCOSE level has DECREASED to 200 (DKA) or 300 (HHS) mg/dL?
Change the IVF’s from NS (or from 1/2 NS “0.45% NS” if serum Na became normal or HIGH) to D5 1/2 NS “5% Dextrose 0.45% NS”
When treating HYPERglycemic CRISES DKA and HYPERglycemic HYPERosmolar Syndrome (HHS) with IV INSULIN BOLUS FIRST, then at a RATE of 0.1 units/kg/hr (while monitoring blood glucose HOURLY) if the BLOOD GLUCOSE does not DECREASE by 10% in the first HOUR, give ANOTHER BOLUS at an INCREASED DOSAGE of 0.14 units/kg and RESUME same RATE. What should you do when the BLOOD GLUCOSE level has DECREASED to 200 (DKA) or 300 (HHS) mg/dL?
REDUCE the RATE to 0.02-0.05 units/kg/hr MAINTAINING the BLOOD GLUCOSE at a level between 150-200 mg/dL until the INCREASED anion gap METABOLIC Acidosis is RESOLVED in DKA (gap is due to the keto acids - the “unmeasured anions”) as there is NO ACIDOSIS in HYPERglycemic HYPERosmolar Syndrome (HHS)
When treating HYPERglycemic CRISES DKA and HYPERglycemic HYPERosmolar Syndrome (HHS) and SERUM K⁺
Give IV KCl 20-30 meq/hr via CENTRAL LINE until K >3.3 meq/L, then ADD 20-30 meq of KCl to EACH LITER of IVF and KEEP SERUM K⁺ between 4.0-5.0 meq/L
When treating HYPERglycemic CRISES DKA and HYPERglycemic HYPERosmolar Syndrome (HHS) and SERUM K⁺ >5.2 meq/L, what MUST YOU DO?
START INSULIN & IVF, DO NOT GIVE K⁺
When treating HYPERglycemic CRISES DKA and HYPERglycemic HYPERosmolar Syndrome (HHS) you notice on the ABG that the pH was 6.9, what do you do?
GIVE Na-BICARBONATE (NaHC03¯) AND KCl over 2 HOURS (DO NOT give sodium bicarbonate if pH >6.9)
BRAIN-MEDIATED ACTIVATION of the PANCREAS, LIVER and ADRENAL GLANDS to RAISE the BLOOD GLUCOSE LEVEL in a state of HYPOglycemia (blood glucose
GROWTH HORMONE (anterior pituitary bg
Why are the SYMPTOMS of sweating, rapid heartbeat, anxiety, hunger (polyphagia) and tremor prevalent in a state of HYPOglycemia (blood glucose
Due to the ACTIVATION of the ADRENAL GLANDS by the brain (via adrenocorticotrophic hormone ACTH) and resulting RELEASE of CATECHOLAMINES epinephrine and norepinephrine
What do the symptoms of cognitive impairment, somnolence, dizziness, impaired speech and change in personality suggest in a DIABETIC?
SEVERE HYPOglycemia and IMPENDING SEIZURES and LOSS of CONSCIOUSNESS as well as focal neurologic signs such as HEMIparesis
In a patient with TYPE 2 DM, EXERCISE before BEDTIME and EtOH consumption can potentially cause what if carbohydrates are not ingested?
HYPOglycemia (liver and muscles take up blood glucose to replenish glycogen after exercise and the liver’s ability to induce gluconeogenesis in the setting of alcohol consumption is impaired)
What is the DANGER in the DIAGNOSTIC process of a TYPE 2 DIABETIC who abuses EtOH?
Attributing HYPOglycemic symptoms to alcohol INTOXICATION
What can occur in a patient with TYPE 1 DM, in patients STRIVING for EXCELLENT GLYCEMIC CONTROL (HbA1c
Their HYPOglycemic SYMPTOMS may NOT be apparent or recognized even by the patient (due to deteriorated response) - treat by reducing insulin dose and increasing carbohydrate intake for a blood glucose level between 150-200 mg/dL to “RESET” the body’s ability to “SENSE”
What is the CHANGE in BLOOD GLUCOSE “NUMBER” between CHANGES of “1.0” in HbA1c?
~28-29 mg/dL (HbA1c of 6.0 - blood glucose of 126; HbA1c of 7.0 - blood glucose of 154; HbA1c of 8.0 - blood glucose of 183) - [183-154=29, 154-126=28, etc.)
When a typical DIABETIC “senses” symptoms of HYPOglycemia (blood glucose
Verify that the BLOOD GLUCOSE is
When a typical DIABETIC has SEVERE symptoms of HYPOglycemia (blood glucose
ANOTHER person should help by ADMINISTERING SUBLINGUAL GLUCOSE (or IV or SQ glucagon, depending on setting)
When does a typical DIABETIC have SYMPTOMS of HYPOglycemia WITH BLOOD GLUCOSE LEVELS >70 mg/dL (can occur at levels at 120 mg/dL or even higher)?
When they are at CHRONICALLY elevated BLOOD GLUCOSE LEVELS (poorly controlled diabetic) >200 mg/dL and then LOWERED closer to the normal range by medications or lifestyle changes (maintaining consistency resets the patient’s symptom threshold)
What is the EARLIEST indication of MICROVASCULAR damage from HYPERglycemia?
RETINAL damage - EDEMA, HARD EXUDATES, TINY HEMORRHAGES - (this is why ALL patients with TYPE 1 DM must be checked by ophthalmologist 5 years AFTER diagnosis, then ANNUALLY and why ALL patients with TYPE 2 DM must be checked AT TIME OF DIAGNOSIS, then ANNUALLY) - in pregnant women with either type of DM, diabetic retinopathy must be SCREENED for in FIRST TRIMESTER and checked EVERY TRIMESTER, then ANNUALLY
Retinal EDEMA, HARD/SOFT EXUDATES, TINY HEMORRHAGES in a diabetic are collectively called?
BACKGROUND or “NON-PROLIFERATIVE” diabetic retinopathy)
Retinal EDEMA, extensive HARD/SOFT EXUDATES, extensive HEMORRHAGES from ruptured blood vessels in a diabetic are collectively called?
PROLIFERATIVE diabetic retinopathy - leads to RETINAL DETACHMENT
What can COMMONLY happen in patients with POOR GLYCEMIC control and in PREGNANT women who are diagnosed with DIABETIC RETINOPATHY and are started on TREATMENT with RAPID IMPROVEMENT in GLYCEMIC CONTROL?
TEMPORARY (reversible) WORSENING of the retinopathy
How are ADVANCED DIABETIC RETINOPATHY and MACULAR EDEMA treated?
LASER PHOTOCOAGULATION (retinopathy) and FOCAL LASER THERAPY (edema)
What LOSS of vision is EXPECTED in LASER treatment for PROLIFERATIVE (neovascularization) DIABETIC RETINOPATHY as a trade off for preventing major retinal bleeding/detachment seen without treatment?
LOSS of PERIPHERAL vision, however CENTRAL vision is preserved
What is an ALTERNATIVE to LASER PHOTOCOAGULATION in patients with PROLIFERATIVE (neovascularization) DIABETIC RETINOPATHY?
INTRA-OCULAR injections of INHIBITORS of Vascular Endothelial Growth Factors (VEGF-I) bevaciZUMAB and ranibiZUMAB every 4-8 WEEKS
How does CHRONIC HYPERglycemia cause KIDNEY INJURY leading to CKD?
HYPERglycemia causes DIRECT, PROGRESSIVE damage to the GLOMERULAR BASEMENT MEMBRANE
What ANNUAL test in ALL patients with DM beginning AT DIAGNOSIS for those with TYPE 2 DM and 5 YEARS AFTER DIAGNOSIS for those with TYPE 1 DM performed to PREVENT DIABETIC NEPHROPATHY and CARDIOVASCULAR DISEASE can result in FALSE ELEVATIONS in the setting of VIGOROUS EXERCISE, MENSTRUATION, ACUTE HYPERglycemia and during ILLNESS?
URINE microalbumin (and protein) using the Urine PROTEIN:Cr (30-300 mg/g indicate microalbuminuria)
What can cause an ACUTE distal SYMMETRIC diabetic neuropathy resulting in a SEGMENTAL DEMYELINATION with a STOCKING-GLOVE distribution?
Episodes of SEVERE HYPERglycemia
Sharp, stabbing, burning PAIN in the toes, feet, lower legs and hands with dysesthesia (discomfort in the skin when touched) and a heaviness/clumsiness in their feet/legs are symptoms seen in DIABETICS with what condition?
PERIPHERAL Diabetic Neuropathy (can cause CARPAL TUNNEL syndrome and MERALGIA PARESTHETICA - numbness in OUTER THIGH)
What is used to treat PERIPHERAL Diabetic Neuropathy BESIDES tight glycemic control?
TOPICAL CAPSAICIN cream, low-dose TCA’s (amitriptyline), SSRI’s/SNRI’s (sertraline, citalopram/venlafaxine, duloxetine)
IF NOT SUFFICIENT with ABOVE, use GABAPENTIN, PREGABALIN, carbamazepine, phenytoin (NO OPIATES)
A form of DIABETIC NEUROPATHY that presents with PROXIMAL LEG WEAKNESS followed by WEIGHT LOSS and PAIN?
Diabetic AMYOTROPHY
What FOOT DEFORMITY can develop in DIABETICS with minor foot trauma, axonal loss and small muscle atrophy?
CHARCOT Foot Deformity (bony degeneration of a weight-bearing joint)
Erectile Dysfunction (50% of men >50 yo), Chronic Diarrhea/Constipation, Orthostatic HYPOtension, Resting Sinus Tachycardia, Postprandial HYPOtension, Sudden Cardiac Death, Abnormal Hidrosis (sweating) and Neurogenic Bladder can ALL be seen in WHOM?
DIABETICS with damage to AUTONOMIC NERVES
What happens in a NORMAL person as BLOOD GLUCOSE LEVELS fall in between meals and fasting?
Pancreas stops secreting insulin and Hepatic glycogenolysis (breakdown of stored glycogen) supplies glucose to maintain BLOOD GLUCOSE LEVELS >70 mg/dL
What organ SECRETES the HORMONE GLUCAGON and what does it do?
The PANCREAS, it STIMULATES the LIVER to break down stored GLYCOGEN into GLUCOSE
What is the EFFECT of GROWTH HORMONE on BLOOD GLUCOSE?
Growth Hormone INHIBITS the actions of INSULIN in states of MODERATE HYPOglycemia (
What is the EFFECT of CORTISOL on BLOOD GLUCOSE?
In MODERATE HYPOglycemia (
What happens during HEPATIC GLUCONEOGENESIS?
PROTIENS (amino acids) and FAT (free fatty acids) are converted into GLUCOSE and KETONES
When does HEPATIC GLUCONEOGENESIS become the ONLY source for GLUCOSE production (by breakdown of proteins and fat) in HYPOglycemic states?
When HEPATIC GLYCOGEN stores are EXHAUSTED - 8 HOURS - (by the pancreatic action of GLUCAGON and the adrenal action of CORTISOL) or by SEPSIS, EXTREME STARVATION, LIVER DYSFUNCTION (alcohol) or CORTISOL and thus ACTH deficiency (ADDISON disease - chronic adrenal insufficiency)
What can cause HYPOglycemic SYMPTOMS in the NORMAL FASTING STATE (in between meals, overnight)?
Insulinoma (VERY RARE), Injecting Insulin (absence of the C-peptide) and taking ORAL Sulfonylureas or Meglitinides (BOTH INDUCE INSULIN secretion by pancreatic β-cells - in which case C-peptide WILL be present)
What is the WHIPPLE TRIAD for DIAGNOSING FASTING HYPOglycemia (SYMPTOMS of HYPOglycemia that occur in between meals, overnight)?
- HYPOglycemic SYMPTOMS are present
2. LOW BLOOD GLUCOSE (
What is done NEXT in searching for the cause of FASTING HYPOglycemia once it is confirmed by the WHIPPLE TRIAD?
INPATIENT 72-HOUR FAST while REGULARLY measuring BLOOD GLUCOSE, PRO-INSULIN (insulin precursor: insulin-C-peptide complex), INSULIN, C-peptide, β-hydroxybutyrate (ketone produced in the absence of insulin) and SULFONYLUREA/MEGLITINIDE levels
- What is found on blood work in the case of FASTING HYPOglycemia if due to an INSULINOMA during the INPATIENT 72-HOUR FAST, once no evidence of surreptitious SULFONYLUREA/MEGLITINIDE ingestion or exogenous insulin injection has been confirmed? 2. What should be done next?
- HIGH LEVELS of BOTH INSULIN and C-peptide (because insulinomas CAUSE the PANCREAS to release too much endogenous insulin)
- CT abdomen/EUS to confirm and SURGERY to remove
What should be done in the case of FASTING HYPOglycemia if it is discovered to be due to surreptitious SULFONYLUREA/MEGLITINIDE ingestion or exogenous insulin injections?
Psychiatric Evaluation
- How do you test someone that has SYMPTOMS of POST-PRANDIAL HYPOglycemia (sleepy, shaky, weak 1-3 hours after large carbohydrate meal) WITHOUT a H/O gastric BYPASS surgery? 2. How do you treat this?
- Observe patient and MEASURE BLOOD GLUCOSE when SYMPTOMS occur, NOT with the oral glucose tolerance test as you MAY INDUCE more SYMPTOMS
- Treat by RECOMMENDING SMALL, FREQUENT meals just as you would for someone who DID have a gastric BYPASS surgery
What is the ONLY PITUITARY HORMONE NOT DECREASED by an INJURY to the PITUITARY STALK (which is the part of the pituitary that receives signals from the HYPOTHALAMUS to RELEASE pituitary hormones) and WHY?
PROLACTIN (because this is the ONLY pituitary hormone whose CONTINUOUS hypothalamic generated signal through the pituitary stalk is an INHIBITORY one via DOPAMINE, whereas for ALL other PITUITARY hormones, the signal is a SECRETORY one)
What occurred in a patient in whom ALL pituitary HORMONES (LH, FSH, GH, ACTH, TSH, ADH, OXYTOCIN) EXCEPT PROLACTIN are DECREASED?
Injury to the pituitary stalk (because PROLACTIN is the ONLY pituitary hormone whose CONTINUOUS hypothalamic generated signal through the pituitary stalk is an INHIBITORY one via DOPAMINE, whereas for ALL other PITUITARY hormones, the signal is a SECRETORY one)
SATIETY and BODY TEMPERATURE regulation are controlled by what structure?
HYPOTHALAMUS (also hypersexuality and somnolence)
What are the most COMMON causes of HYPOpituitarism?
PRIMARY pituitary TUMORS and their TREATMENT (surgery, radiation) followed by EXTRA-PITUITARY lesions (meningioma, germinoma, craniopharyngioma, Rathke cleft cyst - congenital)
What INFILTRATIVE diseases most COMMONLY affect the PITUITARY gland resulting in HYPOpituitarism?
HEMOCHROMATOSIS, LANGERHAN’s Cell Histiocytosis (a lymphoproliferative disease where abnormal “Langerhan cells” proliferate from bone marrow and also affect SKIN with face/chest/abd rash and LYMPH NODES), TB, SARCOIDOSIS
What are PITUITARY APOPLEXY (tumor-caused) and SHEEHAN SYNDROME (blood loss/hypotension DURING CHILDBIRTH - “SHE couldn’t HANdle it”)?
Vascular diseases that cause INFARCTION (subarachnoid hemorrhage can do this as well) of the PITUITARY resulting in HYPOpituitarism
An AUTOIMMUNE disorder that OCCURS in the setting of ACTH deficiency (ADDISON disease, etc.) and PREGNANCY (during or after) p/w HYPOpituitarism due to the SYMMETRIC ENLARGEMENT of the SELLA TURCICA?
LYMPHOCYTIC HYPOPHYSITIS
LYMPHOCYTIC HYPOPHYSITIS, PITUITARY APOPLEXY and SHEEHAN SYNDROME all have WHAT in common?
HYPOpituitarism
SUDDEN ONSET HA and DIPLOPIA with ACUTE HYPOpituitarism (AMS, electrolyte abnormalities, body temperature changes, HR changes) is a SURGICAL EMERGENCY in this condition?
Pituitary APOPLEXY (tumor-caused infarct/hemorrhage into the pituitary)
Besides SURGICAL management for PITUITARY APOPLEXY (tumor-caused infarct/hemorrhage into the pituitary), what is the MEDICAL MANAGEMENT?
- GLUCOCORTICOID REPLACEMENT due to ACTH deficiency (HYDROCORTISONE) and IVF’s - DEXTROSE
- Replacement of TSH, LH, FSH and GH are NOT emergent)
A woman presents S/P delivery in which she was HYPOtensive, with symptoms of inability to lactate and amenorrhea?
SHEEHAN SYNDROME (blood loss/hypotension DURING CHILDBIRTH - “SHE couldn’t HANdle it”)
What is the most COMMON cause of MORTALITY in patients with HYPOpituitarism such as seen in SHEEHAN SYNDROME?
CENTRAL (CNS) ADRENAL INSUFFICIENCY (due to ACTH deficiency)
When PROGRESSIVE HYPOpituitarism is seen in a patient who has a H/O brain lesion s/p treatment, what is the cause?
RADIATION therapy
OF ALL PITUITARY HORMONES, the DEFICIENCY of WHICH ONE HORMONE is ACUTELY LIFE THREATENING and WHY?
ACTH deficiency, because of associated CORTISOL deficiency (hydrocortisone) and ALDOSTERONE deficiency
What is the effect of GROWTH HORMONE DEFICIENCY in ADULTS (short-stature in children - dwarfism)?
LOSS of MUSCLE, INCREASED FAT, LOSS of STRENGTH and STAMINA, DECREASED BONE DENSITY, INCREASED cardiovascular RISK
What is the MINERALOCORTICOID produced by the outermost ADRENAL CORTEX?
ALDOSTERONE (rening-angiotensin-aldosterone)
What is the GLUCOCORTICOID produced by the middle ADRENAL CORTEX?
CORTISOL (hydrocortisone) - replaced by PREDNISONE and other steroids
What is produced by the innermost ADRENAL CORTEX?
TESTOSTERONE (although only ~10% in men as the rest is produced by the testicles)
What is produced by the ADRENAL MEDULLA?
CATECHOLAMINES (EPInephrine and NOREPInephrine)
What is the most COMMON PITUITARY HORMONE DEFICIENCY seen after NEUROSURGERY or RADIATION THERAPY for a lesion in the SELLAR (sella turcica) region?
Growth Hormone (GH) - LOSS of MUSCLE, INCREASED FAT, LOSS of STRENGTH and STAMINA, DECREASED BONE DENSITY, INCREASED cardiovascular RISK and DECREASED QUALITY OF LIFE (decreased sensation of “well being”)
How is Growth Hormone (GH) DEFICIENCY tested for?
By testing for the level of Insulin-like Growth Factor 1 (IGF-1) which is what the LIVER makes after exposure to GH by the PITUITARY gland - IT WOULD BE LOW or testing for GHRH (growth hormone releasing hormone), glucagon or arginine
When the PITUITARY gland produces LESS LH and FSH) the result is HYPOgonadotropic HYPOgonadism (reduced ESTROGEN production and reduced OVULATION) as well as (reduced TESTOSTERONE and SPERM) resulting in what SYMPTOMS?
Amenorrhea, Breast Atrophy, Vaginal Dryness, Reduced Libido, Erectile Dysfunction, Loss of Muscle/Bone Mass and Anemia (men) AND possible GALACTORRHEA (if HYPERprolactinemia is the cause as it suppresses GnRH secretion by the hypothalamus and thus suppressed LH and FSH secretion by the pituitary)
When WOMEN EXERCISE HEAVILY, LOSE significant WEIGHT, SEVERELY RESTRICT their DIET (anorexia), have SIGNIFICANT STRESS/ILLNESS what hormone-associated deficiency can occur?
DECREASED LH and FSH resulting in HYPOgonadotropic HYPOgonadism (reduced ESTROGEN production and reduced OVULATION, OSTEOPOROSIS)
If a patient presents with SYMPTOMS of Amenorrhea, Breast Atrophy, Vaginal Dryness, Reduced Libido, Erectile Dysfunction, Loss of Muscle/Bone Mass, Galactorrhea and HYPOgonadotropic HYPOgonadism is suspected and confirmed by DECREASED LH and FSH, what should be done next?
MRI or CT of the head (look for a lesion)
When does HYPOgonadotropic HYPOgonadism (reduced ESTROGEN production and reduced OVULATION) as well as (reduced TESTOSTERONE and SPERM) occur with SYMPTOMS of GALACTORRHEA?
When it is caused by or there is concomitant HYPERprolactinemia (suppresses GnRH secretion by the hypothalamus and thus suppressed LH and FSH secretion by the pituitary)
When there is a TSH deficiency in the setting of HYPOpituitarism, how is this treated and adjusted?
Treated with LEVOTHYROXINE and progress checked with T4 levels and CLINICAL SYMPTOMS, NOT TSH (as TSH is not released by the pituitary in this condition)
When there is an ACTH deficiency in the setting of HYPOpituitarism, how is this treated and adjusted?
Treated with HYDROCORTISONE or PREDNISONE, adjusted clinically
- When there is a LH/FSH deficiency in the setting of HYPOpituitarism, how is this treated in MEN? 2. Women?
- MEN: TESTOSTERONE (and injected LH/FSH if FERTILITY is desired)
- WOMEN: low-dose COMBINED oral contraceptives or estrogen/medroxyprogesterone (and injected LH/FSH if FERTILITY is desired)
What MUST be done for BOTH MEN and WOMEN in the setting of LH/FSH deficiency due to HYPOpituitarism in ADDITION to supplementation of ESTROGEN/PROGESTERONE (women) and TESTOSTERONE (men) if FERTILITY is DESIRED?
Injected LH/FSH
When there is a GH deficiency in the setting of HYPOpituitarism, how is this treated and adjusted?
Treated with GH supplementation, adjusted to maintain IGF-1 levels in the mid-normal range (higher doses for women on oral estrogens)
When there is an ADH (vasopressin) deficiency in the setting of HYPOpituitarism, how is this treated?
Treated with DESMOPRESSIN (vasopressin “ADH” analogue)
How does the HYPOTHALAMUS STIMULATE the POSTERIOR PITUITARY gland to SECRETE either ADH (vasopressin) or OXYTOCIN?
VIA direct NEURAL stimulation, NOT through a “hormone-releasing-hormone” as is done for the anterior pituitary hormones
What are the SERUM levels of ACTH and CORTISOL when there is an ACTH DEFICIENCY?
LOW/NORMAL ACTH and LOW CORTISOL (because the LOW cortisol level, although signaling the HYPOTHALAMUS to release CRH so that the PITUITARY RELEASES ACTH, however because either something is wrong with the hypothalamus or the pituitary, ACTH is not increased and CORTISOL is low)
What is the SERUM ACTH level when there is a PRIMARY ADRENAL INSUFFICIENCY?
HIGH! (because the LOW cortisol level signals the HYPOTHALAMUS to release CRH so that the PITUITARY RELEASES ACTH and both the hypothalamus and pituitary are normal)
SKIN PIGMENTATION occurs with what HORMONAL abnormality?
ADDISON Disease - PRIMARY ADRENAL INSUFFICIENCY due to the effects of ELEVATED ACTH
A patient with dark skin pigmentation on lips and buccal mucosa, gingiva presents with malaise, weakness, fatigue and HYPOtension and HYPERkalemia, what does he have?
ADDISON Disease - PRIMARY ADRENAL INSUFFICIENCY due to the effects of ELEVATED ACTH
Why does a patient with ACTH deficiency (not primary adrenal issue) and therefore a problem with the HYPOTHALAMUS or PITUITARY not present with HYPOtension or HYPERkalemia?
Because the ALDOSTERONE produced in the outermost portion of the ADRENAL CORTEX is NOT CONTROLLED by the HYPOTHALAMUS/PITUITARY but SEPARATELY by the KIDNEYS/LUNGS/LIVER renin-angiotensin-aldosterone system
HIGH ACTH with HYPOtension and HYPERkalemia?
ADDISON Disease - PRIMARY ADRENAL INSUFFICIENCY
What is the most COMMON cause of ACTH deficiency (disturbance in the hypothlamic-pituitary axis)?
Suppression of the secretion of CRH (hypothalamus) and therefore ACTH (pituitary) by EXOGENOUS CORTICOSTEROID administration (prednisone, megestrol - appetite stimulant used in HIV and cancer patients, etc.) >2-3 WEEKS
How can you tell that ACTH deficiency is NOT due to MEDICATION (corticosteroids) use?
Because OTHER pituitary hormones would ALSO be deficient, not JUST ACTH
How can you tell if HYPOthyroidism is due to a CENTRAL (CNS) cause?
By measuring the SERUM TSH (NORMAL/low) AND T4 (LOW) which would be due to understimulation of the THYROID gland due to a LOW TRH (hypothalamic) or TSH (pituitary) issue where these should be HIGH if the T4 was low (NEED BOTH TSH and T4)
Fatigue, Weight GAIN, COLD-intolerance, CONSTIPATION, BRITTLE hair, dry skin, edema, MOOD changes, poor short-term MEMORY and CONCENTRATION, DEPRESSION, SLOW REFLEXES?
HYPOthyroidism
How can you tell if HYPOthyroidism is due to a PRIMARY (THYROID) cause?
Without a concomitant central cause, the TSH level would be HIGH (T4 and T3 would be low but not necessary) as the properly-functioning hypothalamic/pituitary axis is trying to STIMULATE an ABNORMAL THYROID gland
When a patient is suspected of having HYPOthyroidism and their measured TSH is NORMAL or LOW, what must also be checked?
Serum T4 - would also be LOW (because this would demonstrate the problem to be CENTRAL - hypothalamic/pituitary)
In starvation, critical illness or patients in intensive care unit who have NORMAL/LOW T4, T3 and TSH but ELEVATED rT3 (reverse T3) have what condition?
EUTHYROID SICK-SYNDROME (thyroid if normal and the lab abnormalities are caused by the sickness)
When does SUBCLINCAL (“partial”) CENTRAL DIABETES INSIPIDUS (DI) become clinically apparent?
During stress such as WATER DEPRIVATION (loss of a patient’s usual access to water) or PREGNANCY (due to placental vasopressinase - a placental enzyme that degrades vasopressin causing the “partial” release of vasopressin to now become insufficient)
In a patient with POLYURIA, serum Na is found to be HIGH-NORMAL or HIGH with a LOWER URINE OSMOLALITY than SERUM OSMOLALITY, what’s the likely problem?
Diabetes Insipidus (DI)
In a patient with POLYURIA, serum Na is found to be
SIADH - look for a cancer
In a patient with POLYURIA, serum Na is found to be NORMAL with a LOW URINE/BLOOD OSMOLALITY, what should be done next?
Water Deprivation test to DIFFERENTIATE between DIABETES INSIPIDUS (DI) and PRIMARY POLYDIPSIA (psychogenic)
What is meant by a PITUITARY micro/macro adenoma?
Pituitary MICROadenoma 1 cm
Are most pituitary tumors functional or non-functional? Of the functional ones, which is the most COMMON?
Most are NON-FUNCTIONAL adenomas
Most COMMON FUNCTIONAL pituitary tumor is the PROLACTINOMA (prolactin >200 ng/mL)
Tumors of the Pituitary, Parathyroid and Pancreas are part of what FAMILIAL syndrome?
Multiple Endocrine Neoplasia - 1 (MEN-1) the 3 P’s
Even when benign (most), PITUITARY adenomas cause what type of problems due to their location and mass effect?
Visual Field Defects (optic chiasm), HEADACHES, compressive effect on the remaining pituitary with HYPOpituitarism
What should ALWYS be done if a MASS in the SELLA TURCICA is incidentally detected on a CT?
FOLLOW-UP with MRI and HORMONAL ANALYSIS (HYPO/HYPER) INCLUDING SERUM PROLACTIN level, check for VISUAL FIELD DEFECTS
MRI, Hormonal Analysis (HYPO/HYPER) and Serum PROLACTIN level, check for VISUAL FIELD DEFECTS?
Tests that MUST be done for ALL masses in the SELLA TURCICA whether found INCIDENTALLY or not
What should be done for a pituitary tumor that is found to be CAUSING HORMONAL CHANGES either because it is FUNCTIONAL (secreting hormones) or due to compression of the pituitary causing HYPOpituitarism?
Hormone Replacement Therapy (HYPOpituitarism) or SURGERY (if functional - except prolactinomas - serum prolactin >200 ng/mL)
What should be done for a pituitary tumor that is found to be neither FUNCTIONAL nor causing MASS effect or HYPOpituitarism?
Serial Follow-up Evaluataions
What is located in the SUPRASELLAR region of the cranium (“above” the sella turcica where the pituitary gland sits)?
The OPTIC CHIASM
Bitemporal hemianopia (can’t see the temporal halves) and Diplopia are visual defects seen with what condition?
Pituitary tumors
A patient with a pituitary tumor reports a SUDDEN EXPLOSIVE HEADACHE, what happened?
Likely hemorrhagic infarction of the tumor (Pituitary Apoplexy)
Is DIABETES INSIPIDUS (DI) caused by PRIMARY pituitary tumors?
VERY RARELY, more commonly due to a NON-PITUITARY lesion such as a CYSTIC TUMOR (craniopharyngioma or Rathke cleft cyst - congenital) or metastases
What is the TREATMENT for ALL SECRETORY PITUITARY tumors and ALL PITUITARY MACROADENOMAS (>1 cm) EXCEPT for which ONE?
SURGICAL RESECTION of ALL Pituitary tumors that are FUNCTIONAL (secrete hormone) or those that are >1 cm (MACROADENOMAS) EXCEPT PROLACTINOMAS (prolactin >200 ng/mL) - treated with DOPAMINE agonists (dopamine inhibits prolactin secretion)
What treatment is provided after a ENDONASAL TRANS-SPHENOIDAL resection of a pituitary tumor if there is RESIDUAL DISEASE, continued HYPERsecretion of hormones or patients CANNOT undergo SURGERY?
RADIATION THERAPY
DOPAMINE AGONISTS are used as FIRST-LINE TREATMENT (NOT SURGERY - because tumors shrink by >50% with medical therapy ALONE) to treat what TUMOR?
PITUITARY Prolactinoma - serum prolactin >200 ng/mL - (cabergoline or bromocriptine)
Pregnancy, Nipple Stimulation, Strenuous Exercise and Food Intake are all PHYSIOLOGIC causes of this hormonal action?
HYPERprolactinemia
What is the most COMMON cause of HYPERprolactinemia that is NOT PHYSIOLOGIC (Pregnancy, Nipple Stimulation, Strenuous Exercise, Food Intake)?
Pituitary Prolactinoma - serum prolactin >200 ng/mL - (benign adenoma)
What are the other FIVE (5) causes of HYPERprolactinemia once a PROLACTINOMA (prolactin >200 ng/mL) and PHYSIOLOGIC HYPERprolactinemia have been EXCLUDED?
Tumor (hypothalamic, sellar) affecting the pituitary STALK, HYPOthyroidism, Cirrhosis, Kidney Failure (Cr
Estrogens, Haloperidol, Risperidone, MAOI’s, TCA’s, Fluoxetine, Opiates, Metoclopramide, Domperidone, Methyldopa, Verapamil and COCAINE can all cause HYPERprolactinemia through what action?
Antidopaminergic (block dopamine secretion which inhibits prolactin secretion)
SERUM PROLACTIN levels CORRESPOND DIRECTLY with PROLACTINOMA SIZE. What SERUM PROLACTIN LEVEL is DIAGNOSTIC for a PROLACTINOMA?
Serum Prolactin >200 ng/mL (normal is 5-20 ng/mL)
What other PITUITARY HORMONE is AFFECTED INDIRECTLY by a PROLACTINOMA or by another cause of HYPERprolactinemia (Tumor (hypothalamic, sellar) affecting the pituitary STALK, HYPOthyroidism, Liver Disease, Kidney Failure (Cr
GH (because HYPOTHALAMIC secretion of GnRH is INHIBITED by the INCREASED SECRETION of HYPOTHALAMIC DOPAMINE (negative inhibitory response to HYPERprolactinemia)
If a patient presents with HYPERprolactinemia without a CLEAR secondary or drug-induced cause, what should be done next?
MRI of the PITUITARY gland
Galactorrhea, Gynecomastia, Oligomenorrhea, Amenorrhea, Hirsutism, Erectile Dysfunction, Decreased Libido, Infertility, HA, Osteopenia and Osteoporosis are all manifestations of this HORMONE oversecretion that WARRANT treatment?
HYPERprolactinemia (treat with dopamine agonists - cabergoline or bromocriptine, NOT SURGERY - as tumors typically shrink by >50% with medical therapy ALONE)
What should be done to treat a PROLACTINOMA (prolactin >200 ng/mL) in a patient that complains of visual field defects caused by its mass effect?
STILL NO SURGERY, treat with dopamine agonists - cabergoline or bromocriptine - as tumors typically shrink by >50% with medical therapy ALONE
