

PE
Diabetic Retinopathy
Diabetic Neuropathy
Diabetic Nephropathy
Foot Ulcers
Neuropathic Arthropathy (Charcot’s Joints)
Necrobiosis Lipoidica Diabeticorum
TABLE 5-1
General Comparison of the Two Types of Diabetes Mellitus
Type 1 | Type 2 | |
Previous terminology | Insulin-dependent diabetes mellitus (IDDM), type I, juvenile-onset diabetes | Non–insulin-dependent diabetes mellitus, type II, adult-onset diabetes |
Age at onset | Usually <30 yr, particularly childhood and adolescence, but any age | Usually >40 yr, but any age |
Genetic predisposition | Moderate; environmental factors required for expression; 35%-50% concordance in monozygotic twins; several candidate genes proposed | Strong; 6%-90% concordance in monozygotic twins; many candidate genes proposed; some genes identified in maturity-onset diabetes of the young |
Human leukocyte antigen associations | Linkage to DQA and DQB, influenced by DRB (3 and 4) (DR2 protective) | None known |
Other associations | Autoimmune; Graves’ disease, Hashimoto’s thyroiditis, vitiligo, Addison’s disease, pernicious anemia | Heterogeneous group, ongoing subclassification based on identification of specific pathogenic processes and genetic defects |
Precipitating and risk factors | Largely unknown; microbial, chemical, dietary, other | Age, obesity (central), sedentary lifestyle, previous gestational diabetes |
Findings at diagnosis | 85%-90% of patients have one and usually more autoantibodies to ICA512/Ia-2/IA-2β, GAD65, insulin (IAA) | Possibly complications (microvascular or macrovascular) caused by significant preceding asymptomatic period |
Endogenous insulin levels | Low or absent | Usually present (relative deficiency), early hyperinsulinemia |
Insulin resistance | Only with hyperglycemia | Mostly present |
Prolonged fast | Hyperglycemia, ketoacidosis | Euglycemia |
Stress, withdrawal of insulin | Ketoacidosis | Nonketotic hyperglycemia, occasionally ketoacidosis |
GAD, glutamic acid decarboxylase; IA-2/IA-2β, tyrosine phosphatases; IAA, insulin autoantibodies, ICA, islet cell antibody; ICA512, islet cell autoantigen 512 (fragment of IA-2).
From Andreoli TE (ed): Cecil Essentials of Medicine, 6th ed. Philadelphia, Saunders, 2005.
Detection and DX of Gestational DM (GDM)


Lab Screening in Diabetics




Treatment
1. Diabetic Ketoacidosis
Diagnosis
PE




TABLE 5-2
Oral Antidiabetic Agents and Monotherapy
Sulfonylureas | Biguanides | α-Glucosidase Inhibitors | Incretin Mimetics | Meglitinides | Dipeptidyl Peptidase-4 Inhibitor | |
Generic name | Glimepiride, glyburide, glipizide, chlorpropamide, tolbutamide | Metformin | Acarbose, miglitol | Exanatide, liraglutide | Repaglinide, nateglinide | Sitagliptin, linagliptin, saxagliptin |
Mode of action | ↑↑ Pancreatic insulin secretion chronically | ↓↓HGP; ↓ peripheral IR; ↓ intestinal glucose absorption | Delays PP digestion of carbohydrates and absorption of glucose | ↑ Insulin secretion | ↑↑ Pancreatic insulin secretion acutely | Potentiates insulin synthesis and release |
Preferred patient type | Diagnosis age >30 yr, lean, diabetes <5 yr, insulinopenic | Overweight, IR, fasting hyperglycemia, dyslipidemia | PP hyperglycemia | Type 2 DM | PP hyperglycemia, insulinopenic | |
Therapeutic effects | ||||||
↓ HBA1c∗ (%) | 1-2 | 1-2 | 0.5-1 | ↓ HBA1c by 0.7 -0.9 | 1-2 | ↓ HBA1c by 0.5% |
↓ FPG∗ (mg/dL) | 50-70 | 50-80 | 15-30 | 40-80 | ||
↓ PPG∗ (mg/dL) | ≈90 | 80 | 40-50 | 30 | ||
Insulin levels | ↑ | — | — | ↑ | ||
Weight | ↑ | —/↓ | — | ↑ | ||
Lipids | — | ↓ LDL ↓↓TG |
— | |||
Side effects | Hypoglycemia | Diarrhea, lactic acidosis | Abdominal pain, flatulence, diarrhea | Nausea, headache, diarrhea | Hypoglycemia (low risk) | |
Dose(s)/day | 1-3 | 2-3 | 1-3 | Variable from daily to weekly | 1-4+ | 1 |
Maximum daily dose (mg) | Depends on agent | 2550 | 150 (<60-kg BW) 300 (>60-kg BW) |
16 (repaglinide) 360 (nateglinide) |
100 | |
Range/dose (mg) | Depends on agent | 500-1000 | 25-50 (<60-kg BW) 25-100 (>60-kg BW) |
0.5-4 (repaglinide) 60, 120 (nateglinide) |
50-100 | |
Optimal administration time | ≈30 min premeal (some with food, others on empty stomach) | With meal | With first bite of meal | Preferably <15 (0-30 min) before meals (omit if no meal) | ||
Main site of metabolism/excretion | Hepatic/renal, fecal | Not metabolized/renal | Only 2% absorbed/fecal | Renal | Hepatic/fecal |
HGP, Hepatic glucose production; IR, insulin resistance; PP, postprandial; PPG, postprandial plasma glucose.
∗ Values combined from numerous studies; values are also dose dependent.
From Andreoli TE (ed): Cecil Essentials of Medicine, 6th ed. Philadelphia, Saunders, 2005.
TABLE 5-3
Types of Insulin
Preparation | Brand | Onset (hr) | Peak (hr) | Duration (hr) | Route |
Insulin aspart | NovoLog† | <0.25 | 1-3 | 3-5 | SC |
Insulin aspart protamine/insulin aspart | NovoLog Mix 70/30† | <0.25 | 1-4 | 24 | SC |
Insulin detemir | Levemir‡ | 1 | None | 24 | SC |
Insulin glargine | Lantus† | 1.1 | None | ≥24 | SC |
Insulin glulisine | Apidra† | ≤0.25 | 1 | 2-4 | SC, IV§ |
Insulin lispro | Humalog† | <0.25 | 1 | 3.5-4.5 | SC |
Insulin lispro protamine/insulin lispro | Humalog Mix 75/25† | ≤0.25 | 0.5-1.5 | 24 | SC |
Humalog Mix 50/50† | ≤0.25 | 1 | 16 | SC | |
Insulin injection regular (R) | Humulin R∗ | 0.5 | 2-4 | 6-8 | SC, IM, IV |
Novolin R‡ | 0.5 | 2.5-5 | 8 | SC, IM, IV | |
Insulin isophane suspension (NPH)/regular insulin (R) | Humulin 70/30∗ | 0.5 | 2-12 | 24 | SC |
Humulin 50/50∗ | 0.5 | 3-5 | 24 | SC | |
Novolin 70/30‡ | 0.5 | 2-12 | 24 | SC | |
Insulin isophane suspension (NPH) | Humulin N∗ | 1-2 | 6-12 | 18-24 | SC |
Novolin N‡ | 1.5 | 4-12 | 24 | SC |
Injectable insulins listed are available in a concentration of 100 units/mL; Humulin R, in a concentration of 500 unit/mL for SC injection only, is available by prescription from Lilly for insulin-resistant patients who are hospitalized or under close medical supervision.
∗ Recombinant (using E. coli).
† Recombinant human insulin analogue (using E. coli).
‡ Recombinant (using S. cerevisiae).
§ IV to be used in a clinical setting under proper medical supervision.
From Ferri FF: Ferri’s Clinical Advisor 2010. Philadelphia, Mosby, 2010.
TABLE 5-4
Regular Insulin (SC) Sliding Scale
Finger Stick Blood Glucose | Mild Scale | Moderate Scale | Aggressive Scale |
<60 | 1 amp (25 g) D50 or orange juice, call MD | 1 amp D50 or orange juice, call MD | 1 amp D50 or orange juice, call MD |
60-150 | No insulin | No insulin | No insulin |
151-200 | No insulin | 3 units | 4 units |
201-250 | 2 units | 5 units | 6 units |
251-300 | 4 units | 7 units | 10 units |
301-350 | 6 units | 9 units | 12 units |
351-400 | 8 units | 11 units | 15 units |
>400 | 10 units, call physician | 13 units, call physician | 18 units, call physician |
From Nguyen TC, Abilez OJ (eds): Practical Guide to the Care of the Surgical Patient: The Pocket Scalpel. Philadelphia, Mosby, 2009.



Labs







Imaging
Treatment

2. Hyperosmolar Non-Ketotic Coma, Honk
Definition
Etiology





Diagnosis
H&P





Labs











Treatment

B. Hypoglycemia
Definition


Etiology



Diagnosis



TABLE 5-5
Hypoglycemia in Nondiabetic Pt. Laboratory Differentiation of Factitious Hypoglycemia and Insulinoma
Lab | Insulinoma | Exogenous Insulin | Oral Hypoglycemic Agents (Sulfonylurea/Meglitinides) |
Plasma glucose | ↓ | ↓ | ↓ |
Serum insulin | ↑ | ↑↑ | ↑ |
Plasma and urine sulfonylureas/meglitinides | Absent | Absent | Present |
C-peptide | ↑ | N/↓ | ↑ |
Treatment

C. Anterior Pituitary Disorders
1. Hypopituitarism
Etiology








Diagnosis
H&P







Baseline Labs




Imaging

Treatment



TABLE 5-6
Tests of Pituitary Insufficiency
Hormone | Test | Interpretation |
Growth hormone (GH) | Insulin tolerance test: Regular insulin (0.05-0.15 U/kg) is given IV and blood is drawn at −30, 0, 30, 45, 60, and 90 min for measurement of glucose and GH. | If hypoglycemia occurs (glucose <40 mg/dL), GH should increase to >5 μg/L.∗ |
Arginine-GHRH test: GHRH 1 μg/kg IV bolus followed by 30-min infusion of l-arginine (30 g) | Normal response is GH > 4.1 μg/L. | |
Glucagon test: 1 mg IM with GH measurements at 0, 60, 90,120, 150 and 180 min | Normal response is GH >3 μg/L. | |
Adrenocorticotropic hormone (ACTH) | Insulin tolerance test: Regular insulin (0.05-0.15 U/kg) is given IV and blood is drawn at −30, 0, 30, 45, 60, and 90 min for measurement of glucose and cortisol. | If hypoglycemia occurs (glucose <40 mg/dL), cortisol should increase by >7 μg/dL or to >20 μg/dL. |
CRH test: 1 μg/kg ovine CRH IV at 8 am with blood samples drawn at 0, 15, 30, 60, 90, 120 min for measurement of ACTH and cortisol | In most normal individuals, the basal ACTH increases twofold to fourfold and reaches a peak (20-100 pg/mL). ACTH responses may be delayed in cases of hypothalamic dysfunction. Cortisol levels usually reach 20-25 μg/dL. | |
Metyrapone test: Metyrapone (30 mg/kg to max 2 g) at midnight with measurements of plasma 11-deoxycortisol and cortisol at 8 am. ACTH can also be measured. A 3-day test is also available. Basal cortisol should be >5-6 μg/dL before test. | A normal response is 11-deoxycortisol >7.5 μg/dL or ACTH >75 pg/mL. Plasma cortisol should fall below 4 μg/dL to ensure an adequate response. | |
ACTH stimulation test: ACTH 1-24 (cosyntropin), 0.25 mg IM or IV. Cortisol is measured at 0, 30, and 60 min. | A normal response is cortisol >18 μg/dL. In suspected hypothalamic-pituitary deficiency, a low-dose (1-μg) test may be more sensitive. | |
Thyroid-stimulating hormone (TSH) | Basal thyroid function tests: free T4, free T3, TSH | Low free thyroid hormone levels in the setting of TSH levels that are not appropriately increased. |
Luteinizing hormone (LH), follicle-stimulating hormone (FSH) | Basal levels of LH, FSH, testosterone, estrogen | Basal LH and FSH should be increased in postmenopausal women. Low testosterone levels in conjunction with low or low-normal LH and FSH are consistent with gonadotropin deficiency. |
GnRH test: GnRH (100 μg) IV with measurements of serum LH and FSH at 0, 30, and 60 min | In most normal persons, LH should increase by 10 IU/L and FSH by 2 IU/L. Normal responses are variable, and repeated stimulation may be required. | |
Clomiphene test: Clomiphene citrate (100 mg) is given orally for 5 days. Serum LH and FSH are measured on days 0, 5, 7, 10, and 13. | A 50% increase should occur in LH and FSH, usually by day 5. | |
Multiple hormones | Combined anterior pituitary test: GHRH (1 μg/kg), CRH (1 μg/kg), GnRH (100 μg) are given sequentially IV. Blood samples are drawn at −30, 15, 30, 60, 90, and 120 min for measurements of GH, ACTH, LH, and FSH. | Combined or individual releasing hormone responses must be evaluated in the context of basal hormone values and may not be diagnostic (see text). |
∗ Values are with polyclonal assays.
From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.


2. Anterior Pituitary Hyperfunction Secondary to Pituitary Neoplasms

H&P
Prolactinomas



GH-Secreting Pituitary Adenoma: Acromegaly


Corticotropin-Secreting Pituitary Adenoma: Cushing’s Disease



Thyrotropin-Secreting Pituitary Adenoma

Diagnosis
Prolactinoma


Acromegaly




Cushing’s Disease





Thyrotropin-Secreting Pituitary Adenoma




Imaging


Treatment
Surgery



RadioRx


Medical
Prolactinoma
Acromegaly

Cushing’s Disease


Thyrotropin-Secreting Pituitary Adenoma


D. Fluid Hemostasis Disorders
1. Diabetes Insipidus (DI)
Definition
Etiology
Central (Neurogenic) DI








Nephrogenic DI




Diagnosis
H&P




Labs




Imaging

Treatment


2. Syndrome of Inappropriate Antidiuretic Hormone (SIADH, SIAD) Secretion
Etiology






Diagnosis
H&P




Labs


Imaging

Treatment




Long-term Rx


E. Thyroid Disorders
1. Interpretation of Thyroid Function Studies

FIGURE 5-2 Diagnostic approach to thyroid testing. N, normal.
TABLE 5-7
Findings in Thyroid Function Tests in Various Clinical Conditions
Condition | T4 | FT4I | T3 | FT3I | TSH | TSI | TRH Stimulation |
Hyperthyroidism | |||||||
Graves’ disease | ↑ | ↑ | ↑ | ↑ | ↓ | + | ↓ |
Toxic nodular goiter | ↑ | ↑ | ↑ | ↑ | ↓ | − | ↓ |
Pituitary TSH-secreting tumors | ↑ | ↑ | ↑ | ↑ | ↑ | − | ↓ |
T3 thyrotoxicosis | N | N | ↑ | ↑ | ↓ | +, − | ↓ |
T4 thyrotoxicosis | ↑ | ↑ | N | N | ↓ | +, − | ↓ |
Hypothyroidism | |||||||
Primary | ↓ | ↓ | ↓ | ↓ | ↑ | +, − | ↑ |
Secondary | ↓ | ↓ | ↓ | ↓ | ↓, N | − | ↓ |
Tertiary | ↓ | ↓ | ↓ | ↓ | ↓, N | − | N |
Peripheral unresponsiveness | ↑, N | ↑, N | ↑, N | ↑ | ↑, N | − | N, ↑ |
-, variable; FT3I, free T3 index; FT4I, free T4 index; TSI, thyroid-stimulating immunoglobulin.
From Tilton RC, Barrows A: In Hohnadel DC, Reiss R (eds): Clinical Laboratory Medicine. St. Louis, Mosby, 1992.
2. Hyperthyroidism
Etiology






Diagnosis
H&P


Labs (Fig. 5-3)




Imaging



FIGURE 5-3 Diagnostic algorithm for hyperthyroidism.

Treatment



Clinical Pearl

3. Thyroid Storm
Diagnosis





Labs

Treatment






4. Hypothyroidism
Etiology


FIGURE 5-4 Diagnostic algorithm for hypothyroidism.
Diagnosis
H&P








Labs (see Table 5-7; Fig. 5-4)




Treatment

Clinical Pearls


5. Subclinical Hypothyroidism




6. Myxedema Coma

Etiology

Diagnosis
H&P







Labs

Treatment



7. Thyroiditis
Classification and Etiology





Labs




Imaging

Treatment




8. Evaluation of Thyroid Nodule
Epidemiology and Risk Factors for Malignancy


W/up, Labs/Imaging






FIGURE 5-5 Diagnostic evaluation of solitary thyroid nodule in euthyroid patient. High risk for malignancy: nodule >2 cm, age <40 years, male sex, regional lymphadenopathy, fixation to adjacent tissues, history of previous head and neck irradiation.
9. Thyroid Carcinoma


TABLE 5-8
Characteristics of Thyroid Cancers
Type of Cancer | Percentage of Thyroid Cancers (%) | Age of Onset (yr) | Treatment | Prognosis |
Papillary | 80 | 40-80 | Thyroidectomy, followed by radioactive iodine ablation | Good |
Follicular | 15 | 45-80 | Thyroidectomy, followed by radioactive iodine ablation | Fair to good |
Medullary | 3 | 20-50 | Thyroidectomy and central compartment lymph node dissection | Fair |
Anaplastic | 1 | 50-80 | Isthmusectomy followed by palliative x-ray treatment | Poor |
Lymphoma | 1 | 25-70 | X-ray therapy and/or chemotherapy | Fair |
From Andreoli TE, Benjamin IJ, Griggs RC, Wing EJ: Andreoli and Carpenter’s Cecil Essentials of Medicine, 8th ed. Philadelphia, Saunders, 2010.


H&P




W/up


Treatment

F. Calcium Homeostasis Disorders
2. Hypercalcemia
Etiology







Diagnosis
H&P





Hx



PE


Labs (Fig. 5-6)





Imaging



FIGURE 5-6 Diagnostic algorithm for hypercalcemia. (From Ravel R: Clinical Laboratory Medicine, 6th ed. St. Louis, Mosby, 1995.)
Treatment
Acute Severe Hypercalcemia (serum Ca ≥13 mg/dL or symptomatic pt)





3. Hypocalcemia
Etiology











Diagnosis
H&P





Labs (Table 5-9 and Fig. 5-7)





FIGURE 5-7 Diagnostic algorithm for hypocalcemia. (From Ferri FF: Ferri’s Best Test: A Practical Guide to Clinical Laboratory Medicine and Diagnostic Imaging, 2nd ed. Philadelphia, Mosby, 2010.)
TABLE 5-9
Laboratory Differential Diagnosis of Hypocalcemia
Diagnosis | Plasma Tests | Urine Tests | Comments | ||||||||
Ca | PO4 | PTH | 25(OH)D | 1,25(OH)2D | cAMP | cAMP After PTH | TmP/GFR | TmP/GFR After PTH | Ca | ||
Hypoparathyroidism | ↓ | ↑ | N/↓ | N | ↓ | ↓ | ↑↑ | ↓ | ↓↓ | N/↓ | Deficiency of PTH |
Pseudohypoparathyroidism | |||||||||||
Type I | ↓ | ↑ | ↑↑ | N | ↓ | ↓ | NC | ↑ | ↑ | N/↓ | Resistance to PTH; patients may have Albright’s hereditary osteodystrophy and resistance to multiple hormones |
Type II | ↓ | N | ↑↑ | N | ↓ | ↓ | ↑ | ↑ | ↑ | N/↓ | Renal resistance to cAMP |
Vitamin D deficiency | ↓ | N/↓ | ↑↑ | ↓↓ | N/↓ | ↑ | ↑ | ↓ | ↓ | ↓↓ | Deficient supply (e.g., nutrition) or absorption (e.g., pancreatic insufficiency) of vitamin D |
Vitamin D–dependent rickets | |||||||||||
Type I | ↓ | N/↓ | ↑↑ | N | ↓ | ↑ | ↓ | ↓ | ↓↓ | Deficient activity of renal 25(OH)D-1α-hydroxylase | |
Type II | ↓ | N/↓ | ↑↑ | N | ↑↑ | ↑ | ↓ | ↓↓ | Resistance to 1,25(OH)2D |
(OH)D, hydroxycholecalciferol D; OH2D, dihydroxycholecalciferol; TmP, renal threshold for phosphorus.
From Moore WT, Eastman RC: Diagnostic Endocrinology, 2nd ed. St. Louis, Mosby, 1996.

Treatment





G. Adrenal Gland Disorders
1. Cushing’s Syndrome
Etiology




Diagnosis
H&P





Labs

FIGURE 5-8 Clinical diagnosis and management of Cushing’s syndrome. (From Cameron AM: Current Surgical Therapy, 10th ed. Philadelphia, Saunders, 2011.)
Imaging


Treatment




2. Primary Adrenocortical Insufficiency (Addison’s Disease)
Etiology






Diagnosis
H&P

Labs (Fig. 5-9)



FIGURE 5-9 Diagnostic algorithm for adrenal insufficiency (Addison’s disease). (From Ferri FF: Ferri’s Best Test: A Practical Guide to Clinical Laboratory Medicine and Diagnostic Imaging, 2nd ed. Philadelphia, Mosby, 2010.)
Treatment
Chronic Adrenocortical Insufficiency




Addisonian Crisis





3. Disorders of Mineralocorticoid Secretion
a. Hypoaldosteronism
Etiology


H&P

Diagnosis
Labs




W/up


Treatment




b. Hyperaldosteronism (Conn’s syndrome)
Etiology



Diagnosis




H&P



Labs

Imaging


Treatment



H. Pheochromocytoma
Definition
Diagnosis
H&P





Labs



Imaging




Treatment


I. Carcinoid Syndrome


Diagnosis
H&P








Labs


Imaging



Treatment




J. Multiple Endocrine Neoplasia
Classification
MEN I (Wermer’s Syndrome)


MEN II (Sipple’s Syndrome, MEN IIA)


MEN III (Multiple Mucosal Neuroma Syndrome, MEN IIB)
