Endocrine Points

1- DM diagnosed >126 or 2h after after 75 gram >200 in two separate occasions or symptos of DM and BS >200.

2- IFG BS 100-125, IGT is 2 hour after 75 gram glucose is 140-199

3- DKA: BS >250, PH, &.3, Hco3 <15, NKH: effective osmolarity > 320, BS > 600 and PH >7.3

4- In DKA: do not follow serum ketones get worse as patient improves. Hydoxybutyrate is converted to acetoactate and acetone.

5- In DKA after intital liter of normal saline add KL 20-30 meq/liter of fluids. Early hyperkalemia may occur with lower body K.

6- In DKA: add IV glucose when BS <200.

7- In NKH: IV normal salin intially before insulin, correcting BS will cause worsening of hypovolemia.

8- In : NKH: volume cones before hypertonicity so use IV normal salin initially then IV ½ NS.

9- In DKA fluid needed about 4-5 liters, In NKH about 7-9 liters.

10- In both check BS q 1 h and electrolytes q 2 h until stable.

11- DM contol goal: BS 80-120 before meals 100-140 at bed time, <180 postprandial and HBA1c 7%.

12- Insulin requirement in type1 0.5 units/Kg BW, in type2 1-2 units/Kg if in insulin alone. ½ of insulin is given as basal insulin and the other ½ as premeals.

13- In NPO patient the correction of hyperglycemia is 1 unit/ 50 mg increment above 180 in type 1 and 1 u/30 mg increment above 180 in type 2.

14- LADA latent autimmune diabetes of adulthood.

15- Metformin and thiazoldiones (stage 3 and 4 CHF) both contraindicated in CHF.

16- Metformin is contraindicated if Cr clearance <60 ml

17- Parathyoridectomy in primary hyperparathyroidism if cr clearance <60 ml.

18- Metformin can be given in old age if cr clearance >60 ml.

19- Thiazolodiones: check LFT’s base line and q 2 months for one years discontinue if LFT’s > 2.5

20- Safer in renal failure is thiazoldiones and meglitidines, less so is glypzide.. Glyburides metabolites have long half life to be avoided.

21- Metfromin, thizoldiones and acrobose no hypoglycemia with monotherapy.

22- Acarbose hypoglycemia is treated with glucose and not sucrose.

23- In type 2 DM intial therapy is metformin if BMI > 25 if <25 sulfonylurea is used or thizoldiones if allergy to sulfa. Pico rather than rosiglitzone.

24- If HbA1c is elevated and preprandial BS are good suspect postprandial hypoglycemia.

25- Metformin lowers LDL and triglycerides with no effect on HDL.

26- Exenatide (Byetta- GLP1 or glucagons like peptide analogue) and pramlintide (symlin- amylin agonist) both stimulate insulin release, inhibit glucagons release and delay gastric emptying. Both drugs are given sq premeals, both are associated with weight loss, both cause nausea.

27- Exanitide decrease HBA1c, increase first phase of insulin secretion, decrease both fsting and postprandial blood glucose.

28- Exenatide is given in type 2.5 micg uints bid to increase after one month to 10 micg bid

29- Exenatide can cause acute pancreatitis.

30- Pramilintide is indicated in patients on insulin type 1 or type 2. Mealtime insulin should be decreased by 50 % to prevent hypoglycemia

31- Pramlintide is given as 2.5 units (15 micg) bid in type1 then increase dose by 15 micg every 3 days to a mximum of 60 micg bid. In type 2 start by 60 micg bid and increase by 15 micg q 3 days to a mximum of 120 micg bid.

32- Pramlintide is contraindicated in symptomatic gastroparesis.

33- Exenatide given with metformin no hypoglycemia.

34- Urine microalbumin and ophthalmologic evaluation are to be preformed annually 5 years after the diagnosis of type 1 and at initial diagnosis of type 2 DM.

35- Exercise within 24 h, fever, infection, marked hyperglycemia, marked hypertension , CHF, pyria, uti and hematuria will cause increase urine albumin so trotline follow up of microalbumin is done after these factors have subsided.

36- ACE inhibitors prevent microalbuminuria, reduce both microa and macroalbuminuria and prevent renal disease progression.

37- Greater than 50% of patients with type 2 DM already have CAD.

38- Most common neuropathies in DM are distal symmetrical sensorimotor and diabetic neuropathy.

39- Intravenous insulin infusion is indicate after MI and major surgeries. Goal of BS is 80-110.

40- Non-critical care units goal of BS control is 110 mg/dl preprandial aand 180 mg maximal glucose.

41- For hypoglycemia unawarness let the blood sugar less tightly control in the 200 for about 2 weeks to allow the automic adaptation to be released and patient can regain diabetic awarness.

42- Glucocoricoids and dopamine suppress TSH.

43- TSH in euthyroid sick is mostly not above 20.

44- Thyrotoxicosis is all diseases cause increase thyroid hormone levels which hyperthyroidism is due to only to secretion from the thyroid gland.

45- Apathetic thyrotoxicosis: weight loss, slow afib, small goiter and depression in eldely are mostly the only signs.

46- FTI correlates highly with FT4.

47- Thyrotoxicosis with decrease radioiodine uptake occur in thyroidits, iodine induced, exogenous thyroxine, struma ovarii (produces thyroxine). While the uptake increase in Graves, toxic, MNG toxic nodule, high TSH in TSH pituitary adenoma, HCG acts as TSH stimulate TSH receptor as in Chorcicarcinoma.

48- Betablockers in thyrotoxicosis will alleviate adrenergic symptoms but not symptoms not related to adrenergic effect as weight loss or myopathy. Best to use is a long-acting cardioselective.

49- Thionamides are used to control T$and T3 to normal level and not TSH since it takes time to normalize. It usually takes 4-12 weeks to get T$ and T# to normal levels.

50- Agranulocytosis occurs in 0.2% with thionamides, reversible in most cases. It occurs almost always within the first 90 days.

51- In thyroid storm thionamides are given before iodine since they work by blocking syntheis of T$ and T3 from iodine given idodine before them would increase intial effect of idodine in increasing syntheis of T# and T4.

52- The only contraindication to radioactive iodine is pregnancy.

53- PTU is preferred in pregnancy and thyroid storm, otherwise methimazole is preferred.

54- If TSH is suppressed and FT4 is normal check T3.

55- T$ replacement is 1.6 micg/Kg.

56- Weight gain is due to hypothyroidsm is only 5-10 pounds.

57- In all forms of hypothyroidism FT4 is low.

58- TSH taget is 0.5-2.0 on T4.

59- Check TSH q 6 weeks.

60- Increase T4 dose may be needed in a patient started on anticonvulsant or estrogens.

61- Patient in estrogen or pregnant check FT4 and Ft3 rather than total T$ and total T3.

62- Subclinical hypothyroidism main effect of treatment ifs decrease LDL.

63- -1 to –2.5 is ostepenia, <-2.5 is osteoprosis, <-2.5 + fracture is severe osteoprosis.

64- Average diet in US contain 600 mg calcium per day. Milk and milk products are roughly 300 mg per serving.

65- All anti-osteoprosis meds work by inhibiting bone resorption except for teriparatide works by increasing bone formation.

66- Calcitonin and raloxifeen are proven to prevent vertebral fractures only while bisphonates and teriparatide prevent vertebral and non-vertebral fractures.

67- Most sensitive test for Paget disease is bone scan.

68- Treatment of Paget disease is indicated to all patients with symptoms or involving axial skeleton or weight bearing long bones.

69- Best for Paget is IV zoledronic acid.

70- Amenorrhea or new irregular periods first test is urine hCG.

71- Turner syndrome and gonadal dysgensis will be increase LH and FSH. Treatment is hromone replacement.

72- In PCO US or LH:FSH ratio are not diagnostic, there is no diagnostic test with high sensitivity and specificity.

73- In amenorrhea check hCG if negative check prolactin, FSH and TSH. If all are OK do progesterone challenge for one week. If withdrawal bleeding occurs it means that the uterus was primed by estrogen likely patient have PCO. If not is likely second to hypothalamopituitary disease or Asherman syndrome. Oral contraceptive which as both estrange and progesterone will induce bleeding in the first and not the second. For the first LH and FSH are checked. If both are low image the pituitary if normal patient is likely have hypothalamic amenorrhea due to stress, anorexia, excessive exercise.

74- ERT is continous for postmenopausal and cyclice for premenopausal.

75- ERT may cause spotting in the first 6 months if bleeding is heavy or first bleeding occur 6 months after ERT to refer for endometrial biopsy.

76- Virilization: deep voice, clitoromegaly, frontal baldness and increase muscles.

77- Sudden rapid vvirilization as wll testosterone level >150 ng/dl almost due to adrenal or ovarian tumors. DHEA-S will be elevated with adrenal tumors.

78- Testesterone 25% from ovaries, 25% from adrenal and 50% from peripheral. convertion of androstendione.

79- DHEA-S is mostly from adrenal cortex 95%.

80- Highly consider malignancy in gynecomastia tht is unilateral, ulcerative, with lymphadenopathy, has discharge or bloody drainge proceed immediately proceed with mammogram +/- US and biopsy.

81- Treatment of gynecomastia is by tamoxifen.

82- Hypogonadism is defined as low testosterone level to the age.

83- Leriche’s syndrome: impotence associated with claudication of lower back, buttocks and thighs.

84- Sudden onset of impotence suggest psychogenic factor.

85- Taladafil has the faster onset and longer duration 36 hours.

86- Case report of sudden blindness due to non-ischemic anterior optic neuropathy occurs with PDF-5 inhibitors.

87- All patients with pituitary adenoma should be asked about family history of hypercalcemia or kidney stones for MEN 1. Perioral hyperpigmentation and cutaneous myxomas suggest Carney complex. The pituitary adenoma in Carney is most likely due to GH secreting tumors.

88- Low IGF1 is not sensitive or specific in the diagnosi of GH deficicny, but quite diagnostic when elevted for GH producing adenoma.

89- T4 given to hypothyroid/hypoadrenal patient due to pituitary disease or auoimmune can cause adrenal crisis since it accelerates the catabolism of cortisol. Thus cortisol to be given first.

90- Pituitary adenomas do not cause DI unless their has been surgical treatment, craniopharyngeoma can cause DI even before surgery.

91- Water deprivation test is continued until urine osmolarity stable for at least 3 hours then DDAVP is injected if urine osm increase by 10% or more it is central DI, if no effect it is nephrogenic DI.

92- In incidental adrenal adenoma ( 1 cm or more) 80% are non-functional bengin adenoma. Biopsy does not differential malignant from bengin. The imaging test of choice is CT with contrast. Biopsy is only indicated in patients with metastasis since the yield is high. Pheo should be rolled out before doing the CT-guided biopsy.

93- In incidental adrenal adenoma: for all patients need to tole out pheochromocytoma by 24 h urine metanphrrines and catcholamines. If thr tumore is vascular or other features suggest pheo do plasma fractionated metanephrines. For obvious Cushing do 24 h urine cortisol. For subclinical Cushing do 1 mg overnight dexamethazone test. If patient is not hypertensive you do not need to check rennin/aldosterone. If initial hormonal evaluation is negative check annually for 4 years the hormones.

94- Adrenal adenoma that is homogeneous, <4cm, smooth border, no calcification, attenuation value < 10 Hu on unhenced CT and rapid contrast washout >50% in 10 minutes is mostly benign.

95- Adrenal mass > 4cm should be removed although only 1 of 8 removed is cancer.

96- Labroscopic adrenalectomy is the procedure of choice for most adrenal masses functioning and non-functioning.

97- In adrenal mass MRI in T2 chows enhancement in cancer or pheo. PET scan is inferior to CT and MRI.. PET scan can be considered in adrenal mass >4 cm that has charaterisitic suspicion of malignancy since it is high sensitive to malignancy. However is less specific 16 % of patients with adrenal adenoma will have uptake.

98- Adrenal mass < 4 cm repeat imaging in 3-6 months if stable yearly for 3 years.

99- K should be normalized before evaluating for hyperaldosteronism.

100- Men are typically asymptomatic when there is DHEA-S excess.

101- Most pheo produce both norepinephrine and epinephrine. Epinephrine only producing is rare usually seen in MEN2.

102- In pheo alpha blockers before betablockers or surgery.

103- In stress a random cortisol level >18 role out adrenal insufficiency. If albumin is less than 2.5 check serum free cortisol level.

104- Hyporeninemic hypoladestronism or type 4 RTA is due to mainly to ACE inhibitors, NSAIDs, cyclosporine, heparin and AIDs.

105- After patient is upright for 3h check aldosterone, rennin and cortisol levels. In hyporenin-hypoaldo levels of renin and aldo will be low and cortisol will be normal. In adrenal insufficnecy rennin will be high and aldosterone and cortisol will be low. That is why in the later you monitor with rennin and you replace with cortisone and florinef.

106- A woman with hyperprolactinemia and amenorrhea role out pregnancy.

107- In panhpopituitrism ACTH is usually the last hormone to be lost and the most life threatening.

108- A man with hypopituitrism and bronze skin role out hemochromatosis

109- In primay empty sella mild hyperprolactinemia occur in 15% commonly the only hormonal finding.

110- Best screening the thyroid is TSH except for pituitary disease FT4.

111- In euthyroid sick the most common abnormality is low T3 level. Reverse T3 is increased.

112- T4 or T3 hormones are not indicated in euthyroid sick.

113- Anti-TPO and thyroglobulin antibodies are positive early in the disease. Are non specific can occur in many thyroid diseases including Reidel thyroiditis.

114- Peitibial myxodema and exophthaloms are pathognomonic of Graves.

115- Most common cause of Cushing and adrenal insufficiency are glucocorticoids.

116- In acute secondary adrenal insufficiency as pituitary apolplexy ATH stim test can be normal since there is no time for for the adrenal to atrophy.

117- In patient with bilateral adrenal hemorrhages remember to test for antiphospholipid antibody syndrome.

118- In hypertension and hypokalemia: increae rennin and aldo occur in secondary aldosternoism, increase aldo and decrease renin in primary aldosteronism decrease both if there is another mineralcorticoid like in congenital adrenal hyperplasia, DOC producing tumor, Cushing, Liddle, 11b-HSD deficiency.

119- In DKA the best treatment for acidosis is Insulin.

120- In DKA continue insulin until the anion gab closes even after the glucose has been normalized if even you need to infuse glucose.

121- In diabetic non-ketotic hperosmolar coma if patient is in coma and serum osm less than 330 patient is likely have another cause for coma.

122- In DKA serum ketones > 5mmol/L and urine ketones are large.

123- For each 100 mg increase of blood sugar or triglycerides over 100 mg/dl add 1.6 to correct for artificially low serum sodium.

124- Isolated hypertriglycerdemia with normal cholesterol occur in lipoprotein lipase deficiency (AR), Apo C2 deffiency (AR) and familial hypertriglycerdemia (AD). More than 2000 in the first two and more than 500 in the third. In all eruptive xanthoma, lipemia retinalis and acute pancreatitis can happen at triglycerides > 1000.

125- Isolated hypercholesterolemia occurs in familial hypercholesterolemia (LDL receptor deficiency- AD) in heterozygous total cholesterol is 275-500 and > 500 in homozygous. Familial defective apo B same cholesterol levels as heterozygous.

126- Elevated cholesterol and triglycerides o both about 250-500 range occur in familial combined hyperlipidemia (AD) and familial dysbetalipoproteinemia (AR). The later is associated with palmar and tubular zanthomata.

127- Glucocorticoids are first line therapy for hypercalcemia due to elevated calcium secondary to vitamin D or vitamin D mediated.

128- In vitamin D intoxication or vitamin D mediated calcium, phosphorus will be high and PTH low. In the frist 25 vitamin D will be elevated and in the second 1,25 vitamin D will be elevted.

129- Lithium increases calcium by shifting set point for calium.

130- Before sending the patient for parthyrodiectomy check urine calcium and role out FHH.

131- Hyperparathyroidism causes the greatest osteopenia at the forearm followed by the hip then the spine.

132- The most common fractures in Paget disease are vertebral crush fractures.

133- Immoblizing patient with Paget disease cause hypercalcemia.

134- In any medullary thyroid cance check for RET protoncogen, 75% have a familial disease. Check also for the gene for patients with bilateral pheos.

135- Complete androgen insensitivity is testicular feminization syndrome XY male genotype with female phenotype raised as females. Absence of uterus, absence of sexual hair and infertility. Incomplete androgen sensitivity phenotype vcareis.

136- In seminephrous tubules failure FSH is elevated LH and testosterone are normal. In lyding cell (gonadal failure) FSH is elevated as well LH and testosterone is low.

137- In type 1 DM who were previously well controlled in insulin and have new onset hypoglycemia tole out adrenal insufficiency or hypothyroidism.

138- Autoimmune polyglandular failure is type 1 APCED and type 2 Schimdt syndreome. The first is due to mutation in AIRE the second is due to HLA-DR3 and DR4. in both there is hypoadrealism, less so hypogonadism, pernsious anemia, vetiligo and autoimmune hepatitis. Type 1 is diagnosed by presence of 2 of 3 hypoadrenalism, hypoparathyroidism, and mucocutaneous candidiasis. Type 2 is diagnosed by the presence of 2 of 3 hypoadrenalism, atoimmune throid disease and type 1 DM

139- Tamoxifen increase bone density 1.2% in LS, Raloxifene increase LS 2.4 LS and 2. estrogen and aledronate increase LS 5-7% In the 20 mcg group, when compared to placebo, BMD increased by 9 and 3 more percentage points in the lumbar spine and femoral neck, respectively

140- In summary, PTH increases spine and hip BMD in a dose-dependent manner. But, relative percent change in BMD per individual may vary considerably for the following reasons:

141- Contradictions of PTH: Patients with primary or secondary hyperparathyroidism should not receive PTH, even if they have low BMD. Patients with pre-existing malignancies, renal stones, gout, or renal insufficiency should not be considered candidates for PTH use. Caution about calcium supplementation is warranted although clinical trials have used at least 500 mg elemental calcium and at least 400 IU of vitamin D per day. Dose reductions are feasible if modest hypercalcemia occurs, although the first step should be to discontinue all calcium and vitamin D, and repeat the serum calcium 24 hours after the last dose of PTH.

142- PTH indications: In men and women with severe osteoporosis (low bone mineral density [T score <-2.5] and at least one fragility fracture) who continue to fracture after one year of bisphosphonate therapy, we suggest human recombinant PTH therapy (Grade 2B). (See "Fracture risk reduction" above). We also suggest PTH therapy for patients with severe osteoporosis who are unable to tolerate any of the available bisphosphonates (Grade 2B). Other candidates for parathyroid hormone include patients who have relative contraindications to bisphosphonates (achalasia, scleroderma esophagus, esophageal strictures).

143- Previous or current bisphosphonate use, particularly alendronate, "blunts" the response to PTH. However there are no data to suggest that discontinuing long-term bisphosphonate therapy requires a latency period before starting PTH. Thus, in patients who are switching from bisphosphonates to PTH, we suggest starting PTH immediately after bisphosphonates are discontinued (Grade 2C). (See "Combination therapy" above).

144- We suggest stopping PTH treatment after a maximum of 24 months, because of concerns about osteosarcomas which have been observed in rats receiving high doses of PTH (Grade 2C). This complication has not been observed in human subjects.

145- For patients at high risk for subsequent fracture after discontinuing PTH, we suggest starting a bisphosphonate after PTH is discontinued (Grade 2B). Raloxifene is an alternative for individuals who are intolerant of the available bisphosphonates. (See "After PTH" above).

146- Monitoring patients on PTH treatment should include measurement of serum calcium, renal function and uric acid prior to initiation of therapy and at least once during their course. (See "Monitoring" above).

147- (WHI), the largest randomized trial performed to date, which has thus far revealed that estrogen-progestin therapy is associated with an increased risk for breast cancer, coronary disease, stroke, and venous thromboembolism [1]. Unopposed estrogen appears to be associated only with an increase risk of stroke. While the absolute risk for any of these complications is very small, the potential harm of long-term combined HRT use for prevention of chronic disease outweighs the benefits.

148- Raloxifene did not increase the risk of endometrial cancer, but it did increase the incidence of thromboembolic disease (RR 3.1 compared with placebo), hot flashes, influenza-like symptoms, peripheral edema, and leg cramps [11,13].

149- However, in a two-year study of 37 premenopausal women at risk for breast cancer, raloxifene significantly decreased lumbar spine BMD by 3.5 percent and total hip BMD by 1.0 percent [24]. The decrease in BMD was associated with an increase in all markers of bone turnover. After stopping raloxifene for one year, BMD increased by 1.4 percent and 1.7 percent in the spine and hip, respectively. Therefore, raloxifene, like tamoxifen, has differential effects on bone in pre- and postmenopausal women.

150- No reduction in the risk of nonvertebral fractures was seen. However, in a post-hoc analysis, a decrease in nonvertebral fracture risk was seen in the subgroup of women with the most severe vertebral fractures at baseline (severity determined by radiographic decrease in vertebral height) [15]. The benefit of raloxifene on BMD and on nonvertebral fracture risk in a subgroup of patients with vertebral fractures was still measurable after seven years of treatment [16].

151- The impact of raloxifene on a number of intermediate markers of coronary heart disease (CHD) risk suggested that raloxifene might lower the risk of CHD [25]. Serum LDL, lipoprotein (a), homocysteine, and plasma fibrinogen are decreased by raloxifene, while triglycerides, C-reactive protein, and plasminogen-activator inhibitor concentrations are unchanged [9,26-28]. Serum HDL is either unchanged or modestly increased [9,26,29]. Raloxifene may also decrease insulin resistance in hyperinsulinemic women [30], and does not appear to affect glycemic control [31].

152- In the RUTH trial described above, raloxifene reduced the risk of invasive breast cancer (HR 0.56; absolute risk reduction 1.2 cases per 1000 women per year). The benefit was primarily due to a decreased risk of estrogen-receptor-positive breast cancers. (See "Coronary heart disease" above and see "Selective estrogen receptor modulators for the prevention of breast cancer", section on RUTH trial).

153- In addition, results from the NSABP STAR (Study of Tamoxifen And Raloxifene) chemoprevention trial suggest that the magnitude of benefit from raloxifene in protecting against the development of invasive (but not non-invasive) breast cancer is similar to that of tamoxifen (see below), but with a lower risk of thromboembolic events and cataracts [36].

154- Raloxifene is a reasonable alternative to tamoxifen for breast cancer chemoprevention in postmenopausal women at high risk for breast cancer. Raloxifene has not been studied for this purpose in premenopausal women, and therefore should not be used in this group.

155- Tamoxifen reduces arterial LDL oxidation and LDL degradation, reflecting an estrogen-agonist effect [54,55]. However, unlike estrogen it does not enhance the endothelium-dependent vasodilation response of atherosclerotic coronary arteries, reflecting its estrogen-antagonist effect

156- Thus, in postmenopausal women both with and without CHD, the use of tamoxifen is not associated with either a beneficial or adverse cardiovascular effect.

157- Unlike estrogen and tamoxifen, raloxifene is not associated with vaginal bleeding, and unlike estrogen, it does not increase the risk of endometrial hyperplasia or cancer [3,36,39-41]. In a secondary analysis of the MORE trial, neither endometrial hyperplasia nor endometrial cancer risk were increased with raloxifene compared to placebo

158- Among women with ER-positive breast cancer, tamoxifen reduces the risk of recurrence and death when given as adjuvant therapy and can provide palliation in those with metastatic disease [59,66]. It may also prevent the development of breast cancer in women at high risk

159- Although early studies failed to document an increased risk of uterine sarcoma in women treated with tamoxifen [67,79,80], long-term follow-up reports have disclosed an increased incidence of uterine sarcoma, particularly malignant mixed Mullerian tumors (MMMTs)

160- Estrogen, raloifene and tamoxifen all increase venous thromboembolism.