Endocrinology

Question 1

Chronic alcoholic patient with HTN and obesity presents with: Concentration of fat in the truncal region Development of small cervicodorsal fat pad Slightly ↑ urine free cortisol level 1 mg overnight dexamethasone suppression test: suppression of a.m. cortisol production What is the diagnosis?

Answer 1

Pseudo-Cushing

Question 2

Young marathon runner with BMI < 18 develops: Amenorrhea Urine pregnancy test: Negative Mild ↓ FSH and LH Normal TSH Normal prolactin What is the diagnosis?

Answer 2

Functional hypothalamic amenorrhea - context of a patient who exercises excessively - Other causes include eating disorders, stress and illness, nutritional disease (e.g., celiac disease), and > 10% loss of body weight. Dx: Clinical + low FSH and LH. May need MRI. Tx: Supportive. Less exercise, more calories, and possibly OCPs

Question 3

Functional hypothalamic amenorrhea. Diagnosis depends on?

Answer 3

Dx: Clinical + low FSH and LH. May need MRI.

Question 4

Type 1 diabetic develops gradual onset: Fever, weakness, nausea, vomiting, sporadic abdominal pain, and tanned skin Alopecia Episodes of hypoglycemia on a previously stable insulin regimen ↓ BP Delayed reflexes ↓ Serum Na, ↑ K, and ↑ TSH Diagnosis?

Answer 4

Polyglandular autoimmune syndrome 2, also called Schmidt syndrome Diagnoses are hypothyroidism and adrenal insufficiency. Explanation These diagnoses can occur together as part of the polyglandular autoimmune syndrome 2, also called Schmidt syndrome. Know that you must replace the cortisol before you replace the thyroid hormone. Hopefully, you recognize the collection of classic signs and symptoms for both adrenal insufficiency and hypothyroidism. Then think about the relationships that you know exist between the 2. Recognize that this patient is not presenting with pituitary disease because the TSH is high, not low, and that the patient is tanned, so the ACTH is high, not low. Therefore, both the thyroid and adrenal diseases are primary. Three failing glands (pancreas, thyroid, and adrenal) suggest a polyglandular syndrome. Dx: Clinical + TSH + electrolytes + cosyntropin test (cortisol does not increase after ACTH). Tx: Replacement of levothyroxine, glucocorticoids, and mineralocorticoids.

Question 5

Schmidt syndrome. Diagnosis depends on?

Answer 5

Dx: Clinical + TSH + electrolytes + cosyntropin test (cortisol does not increase after ACTH).

Question 6

What is the reason for the tanned appearance in Schmidt syndrome?

Answer 6

ACTH is high

Question 7

Three failing glands (pancreas, thyroid, and adrenal) suggest a ________ syndrome.

Answer 7

Three failing glands (pancreas, thyroid, and adrenal) suggest a polyglandular syndrome.

Question 8

Positive cosyntropin test

Answer 8

Cortisol does not increase after ACTH.

Question 9

In Schmidt syndrome, what is the pre-treatment trigger?

Answer 9

Replace the cortisol before you replace the thyroid hormone.

Question 10

Postmenopausal female on no meds presents with: Headaches and loss of peripheral vision Weight gain, constipation, alopecia Delayed reflexes ↓ Serum Na+ ↓ FSH and LH What is the diagnosis?

Answer 10

pituitary tumor causing mass effect, hypogonadism, and secondary hypothyroidism. Clues to a diagnosis of thyroid disease: weight gain, constipation, alopecia, delayed reflexes, hyponatremia, and the decreased gonadotropins. FSH and LH in a postmenopausal female are increased, not decreased. The presence of multiple endocrine derangements (thyroid disease + low gonadotropins) and headaches with vision loss suggest that the diagnosis is in the pituitary. Dx: Brain MRI + serum levels of pituitary hormones to screen for excess or deficiency is done for all tumors > 1 cm. Tx: Nonfunctional tumors that do not produce hormones but cause neurologic impairments are referred for transsphenoidal resection + replacement of deficiencies.

Question 11

FSH and LH in a postmenopausal female are __creased, not __creased.

Answer 11

FSH and LH in a postmenopausal female are increased, not decreased.

Question 12

Rx: nonfunctional pitituary tumor

Answer 12

Transphenoidal resection + hormone replacement

Question 13

Highest LR+ for signs of hypothyroidism

Answer 13

• coarse skin - bradycardia - delayed ankle reflex C: The combination of signs that had the highest likelihood ratios (c) was associated with modest accuracy (LR+ 3.75; LR- 0.48).

Question 14

Patient with diabetes ± warfarin use develops: Acute onset of headache Bitemporal hemianopsia ± Neck stiffness ± Confusion or loss of consciousness MRI: High density mass in the sella What is the diagnosis?

Answer 14

Pituitary apoplexy. Explanation The clue that the problem is in the pituitary is the presence of the bitemporal hemianopsia, which suggests a problem around the area of the optic chiasm. Compromise of vascular supply due to growth of adenoma usually is associated with antecedent adenoma symptoms, but hemorrhage into the gland usually is not. Dx: Brain MRI. Tx: Emergent glucocorticoids + neurosurgery consult.

Question 15

Bitemporal hemianopsia suggests a problem near the ___ ___.

Answer 15

Bitemporal hemianopsia suggests a problem near the optic chiasm.

Question 16

Compromise of vascular supply due to growth of adenoma usually is associated with antecedent adenoma symptoms, but _____ into the gland usually is not.

Answer 16

Compromise of vascular supply due to growth of adenoma usually is associated with antecedent adenoma symptoms, but hemorrhage into the gland usually is not.

Question 17

Rx: pitituary apoplexy

Answer 17

Glucocorticoids+ emergency Surgery

Question 18

The management of pituitary apoplexy includes emergency neurosurgical consult and ____

Answer 18

Glucocorticoids

Question 19

Patient with +FH of MEN1 develops: Diabetes Weight loss Chronic diarrhea A beefy red tongue and cheilitis A painful, pruritic blistering rash What is the diagnosis?

Answer 19

Glucagonoma Explanation Dx: Clinical + serum glucagon concentration (> 500 pg/mL) + measurement of multiple molecular weight forms of glucagon + imaging to localize tumor (helical CT or MRI of abdomen) with biopsy. Tx: Surgical resection, if localized. Difficult and specialized treatment if metastases are present at diagnosis. All patients need good nutritional support.

Question 20

Glucagonoma: Dx features

Answer 20

Clinical + serum glucagon concentration (> 500 pg/mL) + measurement of multiple molecular weight forms of glucagon + imaging to localize tumor (helical CT or MRI of abdomen) with biopsy.

Question 21

Tx: Glucagonoma

Answer 21

Surgery C: Surgical resection, if localized. Difficult and specialized treatment if metastases are present at diagnosis. All patients need good nutritional support.

Question 22

Patient presents with gradual onset: Weight gain Cold intolerance Constipation Alopecia Galactorrhea Amenorrhea Coarse hair Periorbital edema Nonpitting ankle edema ↓ HR and delayed reflexes ↓ Hgb and Hct with normal MCV and MCHC ↓ Serum Na ↑ Total cholesterol and serum prolactin ↑ TSH and ↓ FT4 What is the diagnosis?

Answer 22

primary hypothyroidism. Explanation Recognize that this script includes some manifestations of hypothyroidism, and then note that symptoms of other potential endocrine abnormalities also are present (galactorrhea and amenorrhea—which suggest hyperprolactinemia). Then, consider the relationship between thyroid disease and the prolactin levels. Remember that hypothyroidism causes hyperprolactinemia. Do not diagnose a prolactinoma until you have looked at the thyroid 1st. The labs tell you that the thyroid problem is not originating in the pituitary because the TSH is high, not low. Dx: Clinical + TSH + FT4. Tx: Replacement of levothyroxine.

Question 23

Why can a patient with primary hypothyroidism have galactorrhea and amenorrhea?

Answer 23

Hypothyroidism causes hyperprolactinemia. Explanation: Hypothyroidism predisposes to hyperprolactinemia. However, basal serum prolactin concentrations are normal in most hypothyroid patients [38], and only the serum prolactin response to stimuli, such as thyrotropin-releasing hormone (TRH), is increased [39]. In the few hypothyroid patients who have elevated basal serum prolactin concentrations, the values return to normal when the hypothyroidism is corrected [40,41]. It is important to recognize hypothyroidism as a potential cause of an enlarged pituitary gland (due to thyrotroph hyperplasia, lactotroph hyperplasia, or both) and hyperprolactinemia, and not to confuse this entity with a lactotroph adenoma. (See “Causes, presentation, and evaluation of sellar masses”.) The mechanism of hyperprolactinemia in hypothyroidism is not known

Question 24

How does hypothyroidism cause enlargement of the pituitary gland?

Answer 24

• thyrotroph hyperplasia - lactotroph hyperplasia It is important to recognize hypothyroidism as a potential cause of an enlarged pituitary gland (due to thyrotroph hyperplasia, lactotroph hyperplasia, or both) and hyperprolactinemia, and not to confuse this entity with a lactotroph adenoma.

Question 25

Middle-aged patient with h/o alopecia and fatigue develops: Confusion Hypothermia, ↓ BP, ↓ HR Delayed reflexes Nonpitting ankle edema ↓ Hgb and Hct with normal MCV and MCHC What is the diagnosis?

Answer 25

Myxedema coma

Question 26

Features of myxedema coma + hypoglycemia suggests _ _ in addition to hypothyroidism.

Answer 26

Adrenal insufficiency

Question 27

Mx: myxedema coma. Trigger

Answer 27

Hydrocortisone T3+T4 Parenteral T3 and T4 replacement + careful administration of IVF and replacement of electrolytes + passive warming + broad-spectrum empiric antibiotics ± parenteral glucocorticoids

Question 28

Why should we think about stress dose steroids in myxedema coma before T4/T3 replacement?

Answer 28

Adrenal insufficiency Explanation: Adrenal insufficiency may be present. Thyroid hormone replacement prior to steroid replacement will cause “decompensation” because of increased metabolism without adequate steroid support.

Question 29

35-year-old female with no PMH, on no medications, develops: ↑ BP ↓ Serum K ↓ Plasma renin activity ↑ Plasma aldosterone concentration What is the diagnosis? What are other names for this condition?

Answer 29

Conn syndrome or bilateral adrenal hyperplasia - alias primary hyperaldosteronism Explanation: Since the patient is hypokalemic, consider causes of secondary HTN regardless of age. Next, interpret the renin and aldo results. Renin is low in states where aldo is in excess as the primary abnormality, such as with an adrenal tumor or hyperplasia. Dx: Clinical + PAC:PRA (ratio of plasma aldosterone concentration to plasma renin activity; > 20 in an adrenal tumor) + measure aldosterone after oral or parenteral sodium load (when adrenal hyperplasia or tumor present, aldo does not suppress after sodium) + CT of the adrenals to assess for bilateral adrenal hyperplasia or an adrenal tumor. Tx: Depends on cause: Treat hyperplasia with aldosterone receptor blocker (aldactone) and send tumors for surgical resection.

Question 30

In states where aldosterone is in excess as the primary abnormality (tumor or hyperplasia), renin concentrations will be __.

Answer 30

In states where aldosterone is in excess as the primary abnormality (tumor or hyperplasia), renin concentrations will be low.

Question 31

What does renin do?

Answer 31

AGT -> AG I Renin cleaving its substrate, angiotensinogen (AGT), to produce the inactive peptide, angiotensin I, which is then converted to angiotensin II by endothelial angiotensin-converting enzyme (ACE).

Question 32

Angiotensin II mediates _______ as well as ___ release from the adrenal gland, resulting in sodium retention and increased blood pressure.

Answer 32

Angiotensin II mediates vasoconstriction as well as aldosterone release from the adrenal gland, resulting in sodium retention and increased blood pressure.

Question 33

What is the difference between the classical view of the RAS and current views?

Answer 33

Several RAS systems Instead of one simple circulating RAS, it is recognized that there are also several tissue (local) renin-angiotensin systems that function independently of each other and of the circulating RAS. In particular, angiotensin II generation at the tissue level by these local systems appears to have physiologic effects that are as important as circulating angiotensin II and, under some circumstances, more important than circulating angiotensin II.

Question 34

Where is renin secreted?

Answer 34

JGA

Question 35

Why does anti-aldosterone therapy work in heart failure?

Answer 35

Existence of local RAS systems in the heart Explanation: local systems, activation of angiotensin II results in harmful effects and target-organ damage that extend beyond vascular and renal hemodynamics to direct tissue actions, including tissue remodeling, endothelial dysfunction, and fibrosis. A more detailed review appears below. (See ‘Tissue renin-angiotensin systems’ below.)

Question 36

PAC/PRA ratio is used to diagnose

Answer 36

primary hyperaldosteronism Explanation: The first test used in patients suspected to have primary hyperaldosteronism measures the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio

Question 37

The mean value for the PAC/PRA ratio in normal subjects and patients with primary hypertension is _ to _, compared with more than _ to _ in most patients with primary aldosteronism

Answer 37

4 10 30 50 Explanation: The mean value for the PAC/PRA ratio in normal subjects and patients with primary hypertension (formerly called “essential” hypertension) is 4 to 10, compared with more than 30 to 50 in most patients with primary aldosteronism

Question 38

Aldosterone is a steroid hormone, “the main mineralocorticoid hormone”, produced by the _ _ of the adrenal cortex in the adrenal gland.

Answer 38

zona glomerulosa Aldosterone is a steroid hormone, “the main mineralocorticoid hormone”, produced by the outer section (zona glomerulosa) of the adrenal cortex in the adrenal gland.

Question 39

Aldosterone causes the conservation of _, secretion of _.

Answer 39

sodium potassium Aldosterone causes the conservation of sodium, secretion of potassium

Question 40

Young female with a history of other autoimmune diseases (e.g., chronic autoimmune hypothyroidism) develops: Amenorrhea Episodes of diaphoresis and heat intolerance Negative pregnancy test ↑ FSH and LH Normal TSH Normal prolactin What is the diagnosis?

Answer 40

(primary ovarian insufficiency )|(premature ovarian failure)

Question 41

Healthy patient presents with: Fatigue Painful swallowing Neck pain Very tender goiter ↓ RAIU What is the diagnosis? And what is the usual cause?

Answer 41

Subacute thyroiditis Viral

Question 42

RAIU is __ in all forms of thyroiditis Increased/Decreased

Answer 42

RAIU is decreased in all forms of thyroiditis

Question 43

What historical feature distinguishes psychogenic polydipsia from nephrogenic polydipsia?ea

Answer 43

Nocturia Explanation: Patients with psychogenic polydipsia do not continue to drink while asleep, so they do not have nocturia; but nocturia is an early symptom of DI.

Question 44

Rx: nephrogenic DI

Answer 44

(Thiazide diuretic) | (Thiazide)

Question 45

What is the response to water restriction in patients with nephrogenic DI?

Answer 45

• Hypernatremia - Persistent low specific gravity urine

Question 46

Patient presents with episodes of: Anxiety Diaphoresis Fogginess that occurs during fasting and resolves with eating Plasma glucose < 55 mg/dL during an episode During hypoglycemia: Normal insulin level Proinsulin > 20% Normal C-peptide

Answer 46

Insulinoma

Question 47

Insulinoma. Rx?

Answer 47

Resection

Question 48

Normal proinsulin, normal insulin, normal C-peptide during hypoglycemia. Causes?

Answer 48

• Sulfonylurea ingestion - Insulinoma

Question 49

_ _ intake is associated with increased insulin and low C-peptide levels.

Answer 49

Exogenous insulin intake is associated with increased insulin and low C-peptide levels.

Question 50

Hypoglycemia workup

Answer 50

• plasma glucose (low) - insulin (normal or high) - proinsulin (normal or high) - C-peptide (normal or increased) - Sulfonylurea screen Explanation: Check during hypoglycemic episode

Question 51

Dx: Anxiety and tremor Gradual onset of anxiety and tremulousness Palpable thyroid nodule Undetectable TSH Thyroid scan = single hot nodule

Answer 51

Toxic adenoma Explanation: hot nodules are rarely associated with malignancy and do not require biopsy. Dx: Clinical exam + TSH + ultrasound + uptake scan. Tx: Radioiodine ablation.

Question 52

Rx: toxic adenoma

Answer 52

• Surgery - Radioiodine therapy Explanation: For patients with toxic adenoma or MNG, surgery or radioiodine rather than prolonged thionamide therapy. Choice depends upon individual patient factors and availability of thyroid surgeons.

Question 53

Dx-process: toxic adenoma

Answer 53

Clinical exam + TSH + ultrasound + uptake scan

Question 54

Fevers and weakness Nausea and vomiting Sporadic abdominal pain Tanned skin ↓ BP ↓ Serum Na, ↑ K, and ↓ glucose ± eosinophilia 60 minutes after cosyntropin, serum cortisol: 7 μg/dL Dx?

Answer 54

primary adrenal insufficiency. Explanation: This patient is tanned because ACTH is increased. If the AI is primary, it is associated with hyperkalemia and tanned skin because all layers of the adrenal cortex are diseased, resulting in mineralocorticoid and glucocorticoid deficiencies. But secondary AI is not associated with hyperpigmentation (because ACTH is low) or hyperkalemia (because the glomerulosa layer of the adrenal cortex is not diseased and continues to be stimulated by the renin-angiotensin system). Keep straight the electrolyte differences in primary AI (hyperkalemia and metabolic acidosis because of deficiencies of both cortisol and aldosterone) and Cushing syndrome (hypokalemic metabolic alkalosis because of excess aldosterone effect). Dx: Clinical + cosyntropin test. Tx: Glucocorticoid and mineralocorticoid replacement.

Question 55

Why are patients with primary adrenal insufficiency tanned?

Answer 55

ACTH increased Explanation: ACTH is a cleavage product of the pro-hormone, proopiomelanocortin (POMC), which also produces other hormones including α-MSH that stimulates the production of melanin.

Question 56

Adrenocorticotropic hormone (ACTH), is a polypeptide tropic hormone secreted by the __ __ gland.

Answer 56

Adrenocorticotropic hormone (ACTH), is a polypeptide tropic hormone secreted by the anterior pituitary gland.

Question 57

Dx-process: primary adrenal insufficiency

Answer 57

Clinical + cosyntropin test

Question 58

Secondary adrenal insufficiency is not associated with hyperkalemia because the _ _ is not diseased and continues to be stimulated by the _-_ system.

Answer 58

Secondary adrenal insufficiency is not associated with hyperkalemia because the zona glomerulosa is not diseased and continues to be stimulated by the renin-angiotensin system.

Question 59

The electrolyte disturbances in primary adrenal insufficiency are due to diminished secretion of c_ and a_.

Answer 59

The electrolyte disturbances in primary adrenal insufficiency are due to diminished secretion of cortisol and aldosterone.

Question 60

A major function of aldosterone is to increase urinary _ secretion. As a result, hypoaldosteronism can be associated with _ and mild metabolic acidosis.

Answer 60

• potassium - hyperkalemia A major function of aldosterone is to increase urinary potassium secretion. As a result, hypoaldosteronism can be associated with hyperkalemia and mild metabolic acidosis.

Question 61

Hypo_ and Hyper_ are the two major electrolyte abnormalities of primary adrenal insufficiency.

Answer 61

• natremia - kalemia Explanation: Hyponatremia and hyperkalemia are the two major electrolyte abnormalities of primary adrenal insufficiency.

Question 62

Aldosterone increases/decreases sodium reabsorption

Answer 62

Aldosterone normally increases sodium reabsorption.

Question 63

In adrenal insufficiency: hyponatremia is mediated by increased release of _ which results in water retention and a reduction in the plasma sodium concentration]. Both cortisol and aldosterone deficiency contribute to this problem.

Answer 63

ADH In adrenal insufficiency: hyponatremia is mediated by increased release of ADH which results in water retention. Both cortisol and aldosterone deficiency contribute to this problem.

Question 64

only _ to _ percent of patients with primary adrenal insufficiency develop hyperkalemia [17-19]. The normokalemia found in many hypoadrenal patients is attributable to aldosterone-independent regulation of potassium secretion by the distal nephron

Answer 64

only 50 to 60 percent of patients with primary adrenal insufficiency develop hyperkalemia [17-19]. The normokalemia found in many hypoadrenal patients is attributable to aldosterone-independent regulation of potassium secretion by the distal nephron

Question 65

Hyponatremia in adrenal insufficiency is rapidly corrected by _ and _ repletion, which shuts off ADH release and allows excess water to be excreted.

Answer 65

Hyponatremia in adrenal insufficiency is rapidly corrected by cortisol and volume repletion, which shuts off ADH release and allows excess water to be excreted.

Question 66

Hospitalized in the ICU: ↓ TSH, ↓ FT4, ↓ FT3

Answer 66

Euthyroid sick syndrome.

Question 67

Secure-dx: Euthyroid sick syndrome

Answer 67

rT3 Explanation: The levels of rT3 increase because its clearance decreases while its production stays the same. The decreased clearance is possibly from lower 5’-deiodinase activity in the peripheral tissue or decreased liver uptake of rT3. Rarely done

Question 68

Postpartum patient develops: Anxiety and tremulousness Nontender goiter +Anti-TPO antibodies What is the diagnosis?

Answer 68

Postpartum thyroiditis.

Question 69

long-term complication includes chronic _, especially in patients with anti-TPO antibodies.

Answer 69

long-term complication includes chronic hypothyroidism, especially in patients with anti-TPO antibodies.

Question 70

Patient presents with gradual onset: Tremulousness Anxiety Weight loss Diffuse muscle weakness Diarrhea Amenorrhea or erectile dysfunction ↑ BP and HR ± atrial fibrillation and exophthalmos ↓ Hgb and Hct with normal MCV and MCHC ↑ Serum Ca and alkaline phosphatase Uptake and scan: Diffusely increased What is the diagnosis?

Answer 70

Graves disease

Question 71

Which antibodies are positive in Grave’s disease?

Answer 71

TRAb Ex: thyrotropin receptor antibodies (TRAb, also called TSI, TBII, or TBI), determination of the radioactive iodine uptake, or measurement of thyroidal blood flow on ultrasonography (table 1).

Question 72

Impaired glucose tolerance

Answer 72

Two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol/l) on the 75-g oral glucose tolerance test. Exp: A patient is said to be under the condition of IGT when he/she has an intermediately raised glucose level after 2 hours, but less than the level that would qualify for type 2 diabetes mellitus. The fasting glucose may be either normal or mildly elevated.

Question 73

Diagnostic criteria DM

Answer 73

One of: 1. 8 hour fasting glucose > 126 2. 2 hour glucose > 200 with 75 g GTT 3. A1C > 6.5 4. Random glucose > 200 + classic symptoms + Re-confirmation (ADA criteria)

Question 74

Necrolytic migratory erythema (NME)

Answer 74

Necrolytic migratory erythema (NME) is a red, blistering rash that spreads across the skin. It particularly affects the skin around the mouth and distal extremities; but may also be found on the lower abdomen, buttocks, perineum, and groin. It is strongly associated with glucagonoma, a glucagon-producing tumor of the pancreas, but is also seen in a number of other conditions including liver disease and intestinal malabsorption

Question 75

Glucagonoma: SymptomsSigns

Answer 75

Diarrhea, neuropsychiatric symptoms and weight loss of 5–15 kg, Necrolytic migratory erythema

Question 76

Glucagonoma:DiagnosticCriteria

Answer 76

Glucagon > 1000 pg/mL Normal: 50–200 pg/mL.

Question 77

MODY

Answer 77

• Age: [10 .. 45] - Lean body - FHx young onset DM - Autosomal dominant - Insulin independent - Absence of antibodies

Question 78

Normal C-peptide level implies insulin independence. Why?

Answer 78

Adequate insulin production

Question 79

Half-life of insulin

Answer 79

3-5 minute

Question 80

Half-life of C-peptide

Answer 80

20-30 minutes

Question 81

Diabetes meds in pregnancy

Answer 81

• Insulin - Metformin - Glyburide Comment: Metformin and glyburide both have evidence

Question 82

Cause of hypogonadism in hemochromatosis

Answer 82

Iron deposition in the pituitary

Question 83

Early SymtpomsSigns of hemochromatosis

Answer 83

• Fatigue - Sexual dysfunction - Arthralgias

Question 84

IGF

Answer 84

— Insulin-like growth factor 1 (IGF-1) — major mediator of growth hormone (GH)-stimulated — somatic growth mediator of GH-independent anabolic processes — small peptide

Question 85

How do glucocorticoids cause hyperglycemia?

Answer 85

• Impairment of glucose transport into cells - Direct impairment of B-cell function

Question 86

Urine N-telopeptide

Answer 86

— assay for bone turnover markers (BTMs). Explanation: assays include bone-specific alkaline phosphatase (BALP), osteocalcin, and N-terminal propeptide of type 1 procollagen (P1NP); markers specific to bone resorption include N-telopeptide of type 1 collagen (NTX), C-terminal telopeptide of type 1 collagen (CTX), and pyridinoline cross-links (table 1). — role in the care of individual patients is not well established

Question 87

Fecal calprotectin

Answer 87

— increased in intestinal inflammation — may be useful for distinguishing inflammatory from noninflammatory causes of chronic diarrhea

Question 88

Glucocorticoid remediable aldosteronism

Answer 88

• aldosterone synthase hyperactivity, is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.

Question 89

Fatigue Headache High blood pressure Hypokalemia Intermittent or temporary paralysis Muscle spasms Muscle weakness Numbness Polyuria Polydipsia Tingling Hypernatraemia Metabolic alkalosis

Answer 89

Features of Glucocorticoid remediable aldosteronism

Question 90

Diagnosis diabetes is a fasting plasma glucose level of _ mg per deciliter (_ mmol per liter) or more or a glycated hemoglobin level of _% or more; the diagnosis requires confirmation by the same or the other test.

Answer 90

126, 7, 6.5 The diagnostic cutoff point for diabetes is a fasting plasma glucose level of 126 mg per deciliter (7.0 mmol per liter) or more or a glycated hemoglobin level of 6.5% or more; the diagnosis requires confirmation by the same or the other test.

Question 91

A fasting glucose level of _ to _ mg per deciliter (5.6 to 6.9 mmol per liter) is consistent with prediabetes

Answer 91

100, 125 mg per deciliter (5.6 to 6.9 mmol per liter) is consistent with prediabetes

Question 92

Causes of spurious results for glycated hemoglobin;

Answer 92

• Hemoglobinopathies - altered red-cell turnover - racial and ethnic differences

Question 93

What is the point of testing both fasting glucose AND A1C?

Answer 93

• appears to identify different groups of patients with diabetes and prediabetes - yet both tests identify patients at similar risk for complications

Question 94

Most appropriate test for ovarian reserve

Answer 94

Day 3 FSH or antimullerian hormone at any stage of the cycle

Question 95

Anti-mullerian hormone

Answer 95

1. Expressed by the preantral and early antral follicles.
2. AMH level reflect size of the primordial follicle pool
3. Best marker of ovarian function
4. Undetectable at menopause
5. Can be measured at any time of the menstrual cycle.

Question 97

Pituitiary.empty-sella

Answer 97

ESS: pituitary gland shrinks or isflattened; the sella turcica fills with CSF

ESS can be found in the workup of pituitary disorders, or as an incidental finding when imaging the brain.

Primary ESS: small anatomical defect above transmits pressure and causes the gland to flatten out on the walls of the sella turcica. Associated with obesity and increase in intracranial pressure in women.

Secondary ESS : injury, surgery, or XRT. Individuals with secondary ESS can develop loss of function.

Mx: depends on what else is seen in the sella and the clinical situation. The presence of a sellar mass, requires evaluation for hormonal hypersecretion and hyposecretion.

In the absence of a sellar mass and clinical evidence of hormonal excess or deficiency, measurement of thyroxine (T4) and early morning cortisol could be performed, but the likelihood is that they will be normal.

Question 98

Why are plain films sufficient for the dx of osteoporosis in patient with kyphosis and loss of height?

Answer 98

Plain films are sufficient to diagnose vertebral fractures.

vertebral fractures ==> osteoporosis

vertebral fractures ==> predicts future fractures

No need for DEXA

Question 99

Thyrotoxicosis.BestTest

Answer 99

Radionuclide scan

Question 100

Thyrotoxicosis vs hyperthyroidism

Answer 100

Thyrotoxicosis is the term used to refer to all conditions associated with increased serum levels of thyroid hormone

Hyperthyroidism usually refers to those diseases in which the thyroid gland is actually synthesizing and secreting excessive thyroid hormones

Question 101

_ disease and _ _ goiter probably account for more than 90% of all hyperthyroidism cases

Answer 101

Graves disease and toxic multinodular goiter probably account for more than 90% of all hyperthyroidism cases

Question 102

Thyroid: Graves: treatment

Answer 102

No ideal treatment for Graves disease: Antithyroid drugs, radioiodine, and surgery are all effective and have specific advantages and disadvantages (Table 38-4)

Question 103

Thyroid: Graves: Drug of choice

Meta: Drug of choice

Answer 103

Methimazole (Tapazole) is the drug of choice

Propylthiouracil (PTU), can cause fulminant hepatic failure; its use should be limited to

1. allergic reaction with methimazole, and in whom surgery or radioactive iodine is not an option
2. Pregnant patients during the first trimester (methimazole is not recommended in the first trimester because of potential to cause rare congenital defects)

▪

Patients with life-threatening thyrotoxicosis or thyroid storm, because of PTU’s ability to inhibit peripheral conversion of T4 to T3

Question 104

Thyrotoxicosis: how does a radionuclide scan help with ddx?

Answer 104

1. Graves: diffuse uptake
2. Toxic nodular: focal uptake

Question 105

Thyroid: Graves

Antibodies specific to Graves

Answer 105

TrAb

Thyrotropin Receptor Antibodies: highly specific, highly sensitive

anti-TPO can be up in other causes of thyroiditis such as Hashimoto

Question 106

Thyroid: Graves: Methimazole

Adverse reaction

Answer 106

reversible agranulocytosis

Question 107

Hyperlipidemia

How frequently should lipid levels be measured in a 40s aged patient with borderline lipids?

Answer 107

4-6 years

Question 108

Reproductive-Endocrinology: Differential diagnosis of pathologic secondary amenorrhea consists of four main types

Answer 108

1. Hyperprolactinemia (e.g., prolactinoma, drugs)
2. Anovulatory (PCOS)
3. Androgen excess (e.g., androgen-secreting tumors)
4. Hypothalamic amenorrhea (e.g., stress, anorexia, excessive exercise

Question 109

Reproductive-Endocrinology: Primary amenorrhea: Causes

Answer 109

testicular feminization and müllerian defects

Question 110

Reproductive-Endocrinology: Testicular-feminization: Karyotype

Answer 110

XY

Caused by androgen insensitivity

XY karyotype

Normal male testosterone levels

Physical features: Breasts and feminine appearance, absence of axillary or pubic hair, and blind-ending vagina

Question 111

Reproductive: Mullerian defects: Xfx

Meta: XFx PhysicalFindings

Answer 111

Imperforate hymen, abnormal cervix, absence of vagina

Question 112

Reproductive-Endocrinology: Causes of primary amenorrhea

Answer 112

1. Chromosomal abnormalities causing gonadal dysgenesis – 50 percent
2. Hypogonadotropic hypogonadism, including functional hypothalamic amenorrhea – 20 percent
3. Absence of parts, müllerian agenesis – 15 percent
4. Transverse vaginal septum or imperforate hymen – 5 percent
5. Pituitary disease – 5 percent
6. Androgen insensitivity due to mutations in the androgen receptor, CAH, and (PCOS)

Chromosomal abnormalities causing gonadal dysgenesis (ovarian insufficiency due to the premature depletion of all oocytes and follicles) – 50 percent

• Hypogonadotropic hypogonadism, including functional hypothalamic amenorrhea – 20 percent
• Absence of the uterus, cervix, and/or vagina, müllerian agenesis – 15 percent
• Transverse vaginal septum or imperforate hymen – 5 percent
• Pituitary disease – 5 percent
• The etiology in the remaining 5 percent of cases includes a combination of disorders, such as androgen insensitivity due to mutations in the androgen receptor, congenital adrenal hyperplasia, and polycystic ovary syndrome (PCOS)

Question 113

Reproductive-Endocrinology: Adhesions and obliteration of the uterine cavity

Answer 113

Asherman syndrome

Question 114

Reproductive-Endocrinology: PCOS: cause

Thought to be caused by stimulatory effects of excess insulin on

Answer 114

ovarian androgen production

Question 115

Reproductive-Endocrinology: PCOS: Rx for hirsuitism

Answer 115

Weight loss and OCP

spironolactone

Our approach to the management of hirsutism is consistent with the 2008 Endocrine Society Clinical Practice Guidelines on Hirsutism, which suggest an estrogen-progestin contraceptive as first-line pharmacologic therapy for most women [8]. In addition, the 2013 Endocrine Society Clinical Practice Guidelines on the Diagnosis and Treatment of Polycystic Ovary Syndrome also suggest OCs as first-line therapy for menstrual irregularities and hirsutism [1]. An antiandrogen is then added after six months if the cosmetic response is suboptimal (see “Treatment of hirsutism”). OCs and an antiandrogen may sometimes be started simultaneously at the outset, particularly when the cutaneous manifestations are particularly bothersome to the patient.

For women with hirsutism and contraindications to OCs, we sometimes use spironolactone alone, but an alternative form of contraception is essential because, if pregnancy occurs, an antiandrogen such as spironolactone could prevent development of normal external genitalia in a male fetus. Spironolactone alone does not regularize menstrual cycles, and in fact, is sometimes associated with menstrual irregularities. Therefore, in women using spironolactone as monotherapy for hyperandrogenism, progestin therapy is often needed. (See ‘Endometrial protection’ above and “Treatment of hirsutism”, section on ‘Antiandrogen therapy’.)

Question 116

Reproductive-Endocrinology: Breast tenderness, galactorrhea: Implies

Answer 116

Prolactin excess: Breast tenderness, galactorrhea

Question 117

Reproductive-endocrinology: Hirsutism, acne, increased muscle mass, clitoromegaly: Implies

Meta: implies, signifies

Answer 117

Androgen excess

Question 118

Reproductive-endocrinology: Hirsuitism: EtiologicTypes

Answer 118

1. Ovarian
2. Adrenal
3. High prolactin
4. Drugs
5. Physiologic

Question 119

Reproductive-Endocrinology: Hirsuitism: Drug-causes

Answer 119

androgens, phenytoin, cyclosporine

Question 120

Reproductive-Endocrinology:

Inherited defects in adrenal cortisol synthesis result in overproduction of other adrenal hormones, including androgens

Answer 120

CAH

Late-onset or nonclassic 21-hydroxylase deficiency is the most common form, occurring in 0.1–1% of women

Question 121

Reproductive-Endocrinology:

Hirsutism begins at menarche

Menstrual irregularities begin in adulthood

Answer 121

CAH

Diagnosis

17-Hydroxyprogesterone will be elevated (stimulation with synthetic ACTH may be necessary to elicit the abnormality)

Treatment

Hydrocorticosone will decrease the excess androgen production

Question 122

Reproductive-Endocrinology:

Sudden onset, rapid course, and/or presence of virilization suggestive of

Meta: should be a Dx question

Answer 122

Malignancy

Question 123

Most common cause of primary hypogonadism in men is

Answer 123

Klinefelter syndrome

Question 124

Male hypogonadism: Causes

Answer 124

Hypergonadotropic and Hypogonadrotropic hypogonadism

Primary Hypogonadism (Hypergonadotropic Hypogonadism)

Trauma to genital organs

Autoimmune destruction

Mumps orchitis

Medications

Cyclosporine

Chemotherapeutic agents

Congenital disorders

Klinefelter syndrome

Bilateral anorchia

Secondary Hypogonadism (Hypogonadotropic Hypogonadism)

1. Chronic illness
2. Medications
3. Opiates
4. Glucocorticoids
5. Leuprolide
6. Prolactinoma
7. Damage to hypothalamus or pituitary
8. Radiation
9. Tumor
10. Trauma
11. Hereditary
12. Hemochromatosis (pituitary iron deposition)
13. Congenital disorders
14. Kallman syndrome

Question 125

Reproductive-Endocrinology: Klinefelter: Karyotype

Answer 125

XXY

Klinefelter syndrome is the most common congenital abnormality causing primary hypogonadism, occurring in approximately 1 in 1000 live male births [1,2]. This syndrome is the clinical manifestation of a male who has an extra X chromosome. The most common genotype is 47,XXY (figure 1), but greater and lesser numbers of X chromosomes have also been reported, resulting in karyotypes such as 48,XXXY and 46,XY/47,XXY mosaicism [3]. 46,XX males also have Klinefelter syndrome; the development of testes in this setting is presumably due to translocation of a small portion of chromosomal material containing the testis-determining factor to an X chromosome.

The 47,XXY genotype results from nondisjunction of the sex chromosomes of either parent during meiotic division, while mosaicism probably results from nondisjunction during mitotic division after conception. The greater the number of extra X chromosomes, the greater the phenotypic consequences, both gonadal and extragonadal [3]:

●Damage to the seminiferous tubules and, usually, damage to the Leydig cells as well. The gonadal manifestations include almost invariably small, firm testes, severely subnormal sperm count, infertility, elevated serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations, variably subnormal serum testosterone concentration and decreased virilization [3,4]. The damage may be increased if the patient also has cryptorchidism, the incidence of which is increased in Klinefelter [5].

●A long bone abnormality, resulting in increased length of the legs, independent of the increased length of both the arms and legs caused by testosterone deficiency.

●A psychosocial abnormality, unrelated to the hypogonadism, which causes difficulty in social interactions throughout life [6] and has been characterized by “marked lack of insight, poor judgment, and impaired ability to learn from adverse experience” [7].

●Impairment of higher level linguistic competence but relative sparing of vocabulary and understanding of language [8].

●Deficit in the ability to sustain attention without impulsivity [8].

●Predisposition to develop morbidities later in life that are unrelated to testosterone deficiency [9]. These include pulmonary diseases such as chronic bronchitis, bronchiectasis, and emphysema [10]; cancers, including germ cell tumors (particularly extragonadal tumors involving the mediastinum) [11], breast cancer [12], and possibly non-Hodgkin lymphoma [13]; varicose veins, leading to leg ulcers [14]; systemic lupus erythematosus, probably due to the extra X chromosome [15]; and diabetes mellitus [16]. (See “Extragonadal germ cell tumors involving the mediastinum and retroperitoneum” and “Breast cancer in men”.)

Question 126

impotence associated with distal aortic atherosclerosis resulting in claudication of the lower back, buttocks, and thighs)

Answer 126

Lehriche syndrome

Question 127

Calcium: PTH: responds to levels of

Answer 127

Ca++, Phos, Mg++

PTH level is responsive to level of ionized calcium in the blood as well as to the levels of phosphate and magnesium

Question 128

Calcium: circulating forms

Answer 128

Ionized, protein-bound, anion-bound

1. “Ionized” or the free form: Maintained in very narrow limits (45%)
2. Bound to protein (albumin and globulin) (40%)
3. Bound to anions (bicarbonate, phosphate, citrate) (15%)

Question 129

PTH: sites-of-action

Answer 129

Bone, Kidney, GI

Question 130

PTH: effect of raising Ca++

Answer 130

Goes down in minutes

Calcium regulates not only the release of PTH but also its synthesis and degradation. In normal subjects, a decrease in serum ionized calcium of as little as 0.1 mg/dL (0.025 mmol/L) results in a large increase in serum PTH concentration within minutes; conversely, an equally small increase in serum ionized calcium rapidly lowers the serum PTH concentration

Question 131

PTH: what does it do to Vitamin D?

Answer 131

25-D -> calcitriol in the kidney

Then transported to kidney, where it is 1-hydroxylated (under the control of PTH) to 1,25-dihydroxyvitamin D; 1,25(OH)2D (calcitriol) is the active form

Question 132

Vitamin D: what does the skin make it from?

Answer 132

7-dehydrocholesterol

Very few foods naturally contain vitamin D; fatty fish and eggs are the exceptions. Dermal synthesis and foods fortified with vitamin D are the major sources of the vitamin. (See ‘Sources’ above.)

Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)

●The Recommended Dietary Allowance (RDA) for vitamin D is 600 international units (units) daily for adults through age 70 years and for children 1 to 18 years of age (table 2). For adults 71 years and older, 800 units (20 micrograms) daily is recommended for the prevention and treatment of osteoporosis. Vitamin D intake and effective sun exposure are often inadequate in older adults. In older adults, particularly those at increased risk of falls and fracture, we suggest supplementation with vitamin D (Grade 2B). We administer 600 to 800 international units daily. (See ‘Requirements’ above and “Calcium and vitamin D supplementation in osteoporosis”.)

●

Question 133

Vitamin D: terminology

Answer 133

1. Cholecalciferol: D3
2. 25-OH-D: D3 after hydroxylation in liver.
3. 1,25-(OH)2-D: After the next hydroxylation in the kidney.
4. Calcitriol: the double hydroxylated form of Vitamin D and the active form.

Only in fatty fish and eggs are the exceptions. Dermal synthesis and foods fortified with vitamin D are the major sources of the vitamin.

●Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)

●

Question 134

Vitamin D: which vitamin D form to given in renal failure?

Answer 134

Calcitriol

Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)

Question 135

Vitamin D: which form to give to folks without sun?

Answer 135

D3

Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be 25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form, 1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See ‘Metabolism’ above.)

Question 136

Calcium: when is a normal calcium actually high?

Answer 136

Hypoalbuminemia

Calcium is bound to albumin (40%); a “normal” total calcium may actually be high if the albumin is low.

0.8 mg/dL for each 1 g by which the serum albumin level is above or below 4 g/dL

Question 137

Calcium: effect of alkalosis

Answer 137

Decreases ionized Ca++

Acid-base status is also important because alkalosis increases calcium binding to albumin, whereas acidosis decreases it

Question 138

Hypercalcemia: main causes

Answer 138

Hyperparathyroidism and cancer

The two most common causes are hyperparathyroidism and malignancy, which make up more than 90% of cases.

Primary hyperparathyroidism

Malignancy

1. Bone metastases
2. Humoral hypercalcemia (related to PTH-rp)
3. Conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D

Granulomatous disease: Sarcoidosis, Tuberculosis

Familial hypocalciuric hypercalcemia

Drugs

Thiazide diuretics (stimulate renal resorption of calcium)

Lithium (changes “set point” of PTH release)

Vitamin A or D intoxication

Immobilization

Other

Thyrotoxicosis

Pheochromocytoma

Adrenal insufficiency

Parenteral nutrition

Question 139

Hypercalcemia: drug-causes

Answer 139

Thiazides, Lithium

Thiazide diuretics (stimulate renal resorption of calcium)

Lithium (changes “set point” of PTH release)

Question 140

Hypercalcemia: genetic cause

Answer 140

FHH

Question 141

Hypercalcemia: PathoMechanism in granulomatous disease

Answer 141

Unregulated synthesis of 1,25(OH)2 vitamin D by granuloma-associated macrophages
Not sensitive to negative feedback suppression by ↑calcium

Question 142

Hypercalcemia: what feature is seen here?

Answer 142

Band keratopathy

Band keratopathy is a corneal disease derived from the appearance of calcium on the central cornea. This is an example of metastatic calcification, which by definition, occurs in the presence of hypercalcemia.[1][

Question 143

Hypercalcemia: how long does it take for ZA to work?

Answer 143

2 days, nadir at 7 days

1. Pamidronate or zoledronate are drugs of choice; potent and effective
2. Calcium level begins to decline within 2 days and hits nadir at 7 days

Question 144

Hypercalcemia: when are steroids useful?

Answer 144

In hypercalcemia due to granulomatous disease

Most useful in treating vitamin D–mediated hypercalcemia (i.e., vitamin D intoxication, granulomatous diseases)

Work via inhibition of 1,25(OH)2D production

Question 145

Hypocalcemia: when fixing also check?

Answer 145

Check Mg

Severe cases (symptomatic patients): IV repletion with calcium gluconate or calcium chloride slowly

Ensure magnesium is also replete

Mild cases: Oral calcium carbonate or calcium citrate; usually vitamin D as well

Question 146

Hypocalcemia: EGK

Answer 146

QT prolongation

Question 147

Osteoporosis: risk factors

Answer 147

1. Personal history of a fragility fracture
2. first-degree relative
3. Thin body habitus (<127 pounds)
4. Current smoking
5. Current use of glucocorticoid therapy for longer than 3 months

Question 148

Osteoporosis: steroid use, how long

Answer 148

3 months

1. Daily 7.5 mg prednisone are required for bone loss to occur
2. Occurs within 3 to 6 months of use

Question 149

Osteoporosis: T-score and Z-score

Answer 149

1. T-score: SDs +/- mean BMD of young adults
2. Z-score: SDs +/- mean BMD of same age and gender

Question 150

Osteoporosis: DEXA: where is it measured?

Answer 150

Hip and spine

Calculates BMD on the basis of tissue absorption of photons from a radionuclide source or x-ray tube

Measures BMD both at axial (spine) and at appendicular (hip) sites

Question 151

Osteoporosis: DEXA: who to screen

Answer 151

1. Women > 65
2. Women with 1 risk factor
3. Men > 70
4. Men with 1 risk factor

All women 65 years of age or older

Women under age 65 years with one or more clinical risk factors

All men 70 years of age or older

Men under age 70 years with one or more clinical risk factors

Aid in decision regarding hormone therapy

Radiologic evidence of osteopenia

Prior osteoporotic fracture

Monitoring therapy for osteoporosis

Question 152

Osteoporosis: which drugs have been proven to reduce hip/non-spine fractures?

Answer 152

alendronate, risedronate, zoledronic acid, teriparatide, denusomab

Question 153

Osteoporosis: follow up

Answer 153

2 years

Reassessment by DXA at 2 years is usually reasonable

Question 154

Pathophysiology: Chaotic osteoclast function with increased bone remodeling (both formation and resorption)

Answer 154

Paget’s

Question 155

Paget’s: why CHF?

Answer 155

Many vascular shunts

High-output congestive heart failure from numerous vascular shunts

Question 156

Paget’s: Rx

Answer 156

Bisphosphonates for severe disease

Question 157

Osteoporosis: FRAX Indications for treatment

Answer 157

P(hip-fracture) > 3% or P(major-fracture) > 20%

f the probability of a hip fracture is 3% or greater and/or the probability of any major osteoporotic fracture is 20% or greater, the patient is a candidate for pharmacotherapy. In this case, the patient’s 10-year risk of hip fracture is 4%, and thus she is a candidate.

Question 158

Hypertriglyceridemia + untreated DM2: why treat DM2 first?

Answer 158

Because it will fix the hypertriglycerides

Question 159

Hypertriglyceridemia:

For patients with triglyceride levels persistently above 886 mg/dL (10.0 mmol/L) after nonpharmacologic interventions, we suggest starting drug therapy to lower the risk of pancreatitis (Grade 2C).

Answer 159

We start therapy with a fibrate.

Question 160

Osteoporosis: when to start bisphosphonates after hip fracture?

Answer 160

Within 1 to 2 months

Theoretical risk of impairing healing in the first 2 weeks

Question 161

Cholesterol: how frequently to screen for borderline hypercholesterolemia in a middle aged person?

Answer 161

4 to 6 years

Question 162

Diabetes: Close control target in the ICU

Answer 162

140 to 180

IV insulin continous

While the optimal blood glucose target is unclear, we suggest a blood glucose target of 140 to 180 mg/dL (7.7 to 10 mmol/L)

While most clinicians agree that such glycemic control is a desirable intervention, the optimal blood glucose range is controversial. (See ‘Glycemic control’ above.)

• For hyperglycemic critically ill children and adults, we recommend against using a stringent intensive insulin therapy regimen to achieve a target blood glucose range of 80 to 110 mg/dL (4.4 to 6.1 mmol/L) ((Grade 1A) for adults;(Grade 1B) for children). While the optimal blood glucose target is unclear, we suggest a blood glucose target of 140 to 180 mg/dL (7.7 to 10 mmol/L) rather than a more stringent target or a more liberal target (eg, 180 to 200 mg/dL [10 to 11.1 mmol/L]) (Grade 2C). This preference is based upon clinical trials in critically ill children and adults that suggest that IIT is not beneficial and is associated with an increased risk of severe hypoglycemia. (See ‘Glycemic control’ above and ‘General approach’ above.)
• To achieve the target blood glucose in adult patients, we minimize use of intravenous fluids (IVF) that contain glucose and administer insulin only when necessary. A widely accepted insulin regimen has not been established but short-acting insulin is preferred. The same basic principles apply in pediatric patients with the exception that children (particularly young children) generally require dextrose in maintenance IVF to ensure adequate glucose delivery to avoid hypoglycemia and provide nutrition. Other sources of glucose (eg, IV medications) should be limited in critically ill children. (See ‘General approach’ above.)
• Careful monitoring of blood glucose is necessary to achieve glycemic control while avoiding the potential harmful effects of hypoglycemia. (See ‘General approach’ above and ‘Hypoglycemia’ above.)

Question 163

Hyponatremia: developing 1 week after trans-sphenoidal resection + normal hormones. Dx/Rx

Answer 163

Dx: SIADH

Rx: Fluid restrict

The SIADH is transient, 7 to 10 days after

Question 164

Adrenal-insufficiency: why is mineralcorticoid replacement not necessary in central adrenal insufficiency?

Answer 164

Aldosterone is regulated by the RAS, primarily.

Hence, levels are adequate

Question 165

Thyroid: Hyperthyroidism: why is methimazole prefered over PTU?

Answer 165

Dosing less frequent, less toxic

Question 166

Thyroid: Hyperthyroidism: Fever+sore throat in a patient on methimazole: Trigger

Answer 166

Check for agranulocytosis

Fever+sore throat: CFx agranulocytosis

Question 167

Agranulocytosis: Rx

Answer 167

Antibiotics

GM-CSF (no evidence)

Question 168

Thyrotoxicosis: FirstTest

Answer 168

Radionuclide scan with I-123 or Tc

Question 169

Thyroid: Graves: serology

Answer 169

Trab

TRAb stimulate the thyroid gland and are specific for Graves’ disease, in contrast to thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies. They bind mainly to the leucine-rich repeat region of the thyroid-stimulating hormone (TSH) receptor (TSHR) ectodomain to which the TSH binds (figure 1). (See ‘Autoantibodies to the TSH receptor’ above.)

Question 170

Post-prandial hypoglycemia after gastric bypass. Rx

Answer 170

Decrease carb content in meals

Late dumping – Less often, patients complain of the same constellation of symptoms hours after eating, so-called late dumping syndrome. This phenomenon is not strictly due to alterations of osmotic gradients across the gastrointestinal (GI) tract, but rather is thought to result from hypoglycemia following a postprandial insulin peak. (See “Postprandial (reactive) hypoglycemia”.)

●Diagnosis – A suggestive pattern of symptoms in a patient who has undergone gastric surgery should raise the possibility of dumping syndrome. The diagnosis of dumping syndrome is made primarily on clinical grounds [11]. A monitored glucose challenge, upper GI series, or gastric emptying studies have been used to support the diagnosis.

●Treatment – Most patients with dumping can be treated conservatively with dietary changes (frequent small meals that are high in fiber and protein and low in carbohydrates, separation of liquid from solid during meals) [9,10]. Symptoms tend to resolve in most patients as they learn to avoid foods that aggravate the problem (eg, simple sugar).

Question 171

Sunitinib: endocrine side effect

Answer 171

Hypothryoidism

Question 172

Gender dysphoria: first-step

Answer 172

Referral to psychiatrist for dx confirmation

Question 173

Primary adrenal insufficiency is its principal manifestation, but autoimmune thyroid disease and type 1 diabetes mellitus are also common. About half of the cases are familial, with polygenic modes of inheritance. It occurs later than type 1, usually presenting by age 40 years.

+ Pernicious anemia

Answer 173

Polyglandular autoimmune syndrome 2

Question 174

Thyroid: frankly elevated TSH

Answer 174

> 10

For patients with subclinical hypothyroidism and TSH concentrations ≥10 mU/L, we suggest treatment with thyroid hormone (T4 [levothyroxine]) (Grade 2B) (algorithm 1). (See ‘Candidates for T4 replacement’ above.)

●For patients with TSH of 7.0 to 9.9 mU/L who are <65 to 70 years, we also suggest treatment with thyroid hormone (Grade 2C). However, for patients >65 to 70 years, we suggest treatment only if they have convincing symptoms of hypothyroidism (algorithm 1). (See ‘Candidates for T4 replacement’ above.)

●For patients with TSH above the upper limit of normal to 6.9 mU/L, we suggest treatment in patients <65 to 70 years who have symptoms of hypothyroidism (Grade 2C). Treatment with T4 can also be considered in such patients with TSH above the upper limit of normal to 6.9 mU/L who have high titers of thyroid peroxidase (TPO) antibodies, which predict progression to overt hypothyroidism, or goiter (algorithm 1). (See ‘Candidates for T4 replacement’ above.)

●For older patients (>65 to 70 years) with subclinical hypothyroidism and TSH above the upper limit of normal to 6.9 mU/L, we suggest not treating (Grade 2C), in view of the uncertain benefits and the potential for both cardiovascular and skeletal morbidity associated with inadvertent overtreatment (algorithm 1). (See ‘Candidates for T4 replacement’ above.)

Question 175

Ectopic ACTH: tumors that make it

Answer 175

Carcinoid, small cell lung cancer

Question 176

Morbid obesity after craniopharyngioma resection: Cause

Meta: Never seen a case

Answer 176

Hypothalamic injury

Question 177

Graves disease: how long to treat with methimazole before tapering?

Answer 177

18 months

Question 178

Gluconeogenesis: sites

Answer 178

Liver and kidney

Hence: nephrectomy can lead to hypoglycemia in a patient on glyburide. This is the reason why glyburide is contra-indicated in reduced GFR.

Question 179

Cushing: SpecificTest

Answer 179

24-hour urinary cortisol or midnight salivary cortisol

For patients with a low index of suspicion, we suggest initial testing with one of the following first-line tests: late-night salivary cortisol (two measurements), 24-hour urinary free cortisol (UFC) excretion (two measurements), or the overnight 1 mg dexamethasone suppression test (DST). (See ‘Initial testing’ above.)

For patients with a high index of suspicion, we suggest initial testing with two of the first-line tests: late-night salivary cortisol (two measurements), 24-hour UFC excretion (two measurements), or the overnight 1 mg DST. (See ‘Initial testing’ above.)

●If UFC is chosen as the initial screening test, the result should be unequivocally increased (threefold above the upper limit of normal for the assay), or the diagnosis of CS is uncertain and other tests should be performed. (S

Question 180

facial plethora, proximal myopathy, striae (>1 cm wide and red/purple), and easy bruising

Answer 180

Cushing

Question 181

Hashimoto: which antibody

Answer 181

Antibodies to Tg and TPO —

Nearly all patients with Hashimoto’s thyroiditis have high serum concentrations of antibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). These antibodies are also found, although usually in lower concentration, in patients with other thyroid diseases including Graves’ disease and in many subjects

Hashimoto’s thyroiditis is characterized clinically by gradual thyroid failure, with or without goiter formation, due primarily to autoimmune-mediated destruction of the thyroid gland involving apoptosis of thyroid epithelial cells. (See ‘Introduction’ above.)

Question 182

Contrast induced hyperthyroidism: which scenario?

Answer 182

Multinodular goiter

Some nodules may be functioning autonomously

Question 183

Adrenal incidentaloma: size for excision

Answer 183

> 4 cm consider, > 6 cm definitely excise

Question 184

Heterogeneous group of patients with variable titers of antibodies, body mass index (BMI), and frequency of progression to insulin dependence [11]. Patients with high compared with low titers of GAD65 antibodies usually have a lower BMI, less endogenous insulin secretion (as measured by stimulated serum C-peptide concentrations), and progress more quickly to insulin dependenc

Answer 184

LADA

Latent autoimmune diabetes in adults (LADA) — Older studies in predominantly Scandinavian populations have suggested that as many as 7.5 to 10 percent of adults in populations with a high prevalence of type 1 diabetes and with apparent type 2 diabetes may have circulating autoantibodies directed against pancreatic beta cell antigens (islet-cell antibodies [ICA] or GAD65) [2-4]. The prevalence of LADA is almost certainly lower in the more diverse United States population. These adults do not require insulin at diagnosis but progress to insulin dependence after several months to years. This entity is sometimes referred to as “latent autoimmune diabetes in adults” (LADA) and may account for a very small fraction of all cases of diabetes [5-7].

Question 185

) is a rare inherited connective tissue disorder with many phenotypic presentations. Severely affected patients suffer multiple fractures with minimal or no trauma; most commonly caused by autosomal dominant mutations in genes encoding the alpha-1 and alpha-2 chains of type I collagen (COL1A1 and COL1A2).

Answer 185

Osteogenesis imperfecta (OI)

Question 186

Diabetes: drugs to avoid in diabetic gastroparesis

Answer 186

GLP-1 agonists and amylin analogues

Question 187

Diabetes: how do GLP-1 agonists work?

Answer 187

Delay gastric emptying

enhancement of glucose-dependent insulin secretion, slowed gastric emptying, regulation of postprandial glucagon, and reduction of food intake (table 1). They do not usually cause hypoglycemia in the absence of therapies that otherwise cause hypoglycemia.

Exact role is unclear

Question 188

Amylin analogue: mechanism-of-action

Answer 188

Slows gastric emptying

Pramlintide regulates postmeal blood glucose levels by slowing gastric emptying, promoting satiety, and suppressing the abnormal postprandial rise of glucagon in patients with diabetes [11-13]. Thus, endogenous (liver-derived) and exogenous (meal-derived) glucose influx are better regulated, allowing exogenous insulin therapy to more easily match physiologic needs.

Question 189

X-linked hypophosphatemia: Rx

Answer 189

Phosphate + calcitriol

Question 190

Elderly man at risk for falls: which supplement?

Answer 190

Vitamin D

Question 191

Reproductive-endocrinology: hormonal contraceptive in patient with hypertriglyceridemia

Answer 191

Progestin-only contraceptive

Eg: depot medroxyprogesterone

Question 192

medullary thyroid cancer (MTC), pheochromocytoma, and primary parathyroid hyperplasia.

Answer 192

MEN2a

Approximately 40% have pheo

Question 193

MEN1 vs MEN2

Answer 193

MEN1: pancreatic neuroendocrine neoplasia, pitutiary tumors

Question 194

Hypercalcemia, hyperphosphatemia + low calcitriol

Answer 194

Milk-alkali syndrome