The American Diabetes Association (ADA) defines DM as follows:• FPG ≥126 mg/dL, which should be confirmed with repeat testing on a different day. Fasting is defined as no caloric intake for at least 8 hr.
• Sx of hyperglycemia and a casual (random) plasma glucose ≥200 mg/dL. Classic sx of hyperglycemia include polyuria, polydipsia, and unexplained weight loss.
• An OGTT with a plasma glucose ≥200 mg/dL 2 hr after a 75-g (100 g for pregnant women) glucose load
• HBA1c ≥6.5%
Prediabetes: glucose levels > nl but not high enough to meet the criteria for dx DM• Impaired fasting glucose: FBS 100 to 125 mg/dL
• Impaired glucose tolerance: after OGTT, a 2-hr plasma glucose 140 to 199 mg/dL
• HBA1c value 5.7% to 6.4%
PE
Diabetic Retinopathy
a. Nonproliferative (background diabetic retinopathy)
i. Initially: microaneurysms, capillary dilation, waxy or hard exudates, dot and flame hemorrhages, atrioventricular shunts
ii. Advanced stage: microinfarcts with cotton wool exudates, macular edema
b. Proliferative retinopathy: formation of new vessels, vitreous hemorrhages, fibrous scarring, and retinal detachment
Diabetic Neuropathy
a. Distal sensorimotor polyneuropathy
i. Sx: paresthesia, hyperesthesia, or burning pain involving bilateral distal extremities, in a “stocking-glove” distribution. It can progress to motor weakness and ataxia.
ii. PE: ↓ pinprick sensation, sensation to light touch, vibration sense, and loss of proprioception. ↓ DTRs and atrophy of interossei muscles can also be seen.
b. Autonomic neuropathy
i. GI: esophageal motility abnlities, gastroparesis, diarrhea (usually nocturnal)
ii. GU: neurogenic bladder (hesitancy, weak stream, and dribbling), impotence
iii. Orthostatic hypotension: postural syncope, dizziness, lightheadedness
c. Polyradiculopathy: painful weakness and atrophy in the distribution of ≥1 contiguous nerve roots
d. Mononeuropathy involving cranial nerves III, IV, or VI or peripheral nerves
Diabetic Nephropathy
Pts have pedal edema, pallor, weakness, uremic appearance.
Foot Ulcers
They occur in 15% of individuals with DM (incidence rate, 2%/yr) → leading causes of hospitalization and amputation in U.S. They result from combination of PVD, repeated trauma (unrecognized because of sensory loss), and superimposed infection.
a. Sx: less than would be expected from clinical findings, resulting from loss of sensation related to peripheral neuropathy
b. Dx: assessment of pedal pulses, sensation (using a 10-g monofilament)
c. Prevention: strict glucose control, pt education, prescription footwear, podiatric care, evaluation for surgical interventions
Neuropathic Arthropathy (Charcot’s Joints)
Bone or joint deformities result from repeated trauma (secondary to peripheral neuropathy).
Necrobiosis Lipoidica Diabeticorum
Plaquelike reddened areas with a central area that fades to white yellow are found on the anterior surfaces of the legs.
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)
OGTT
Women with GDM should be screened for diabetes 6 to 12 wk post partum.Lab Screening in Diabetics
Screening for diabetic retinopathy: Alb/Cr ratio (microalb) in a random spot urine collection or by 24-hr urine collection for alb, CrCl
Dx of microalbuminuria (30-299 mg/24 hr) should be based on 2 to 3 ↑ levels within a 3- to 6-mo period because of marked variability in day-to-day alb excretion
Labs in DM: HBA1c, urine microalbumin, fasting lipid panel, serum Cr, and electrolytes; TSH, vitamin B12 level, IgA TTG Ab (for celiac disease screen) in type 1 DM
Daily monitoring with glucose test strips: type 1 DM and pregnant women on insulin ≥3 ×/day. T2 DM not on insulin, 1-2×/dayTreatment
ADA and European Association for the Study of Diabetes recommend: “Intervention at the time of Dx with metformin in combination with life style changes (diet and exercise) and continuing timely augmentation of Rx with additional agents (including early initiation of insulin Rx) as a means of achieving adequate glycemic control
1. Diet
a. Calories
i. Start with 15 calories/lb of ideal body weight; ↑ 20 calories/lb for an active person and 25 calories/lb if the pt does heavy physical labor.
ii. The calories are distributed as 45% to 65% carbohydrates; <30% fat, with saturated fat limited to <7% of total calories; and 10% to 30% protein; daily cholesterol <300 mg.
iii. The emphasis should be on complex carbohydrates rather than simple and refined starches and on polyunsaturated instead of saturated fats in a ratio of 2:1.
iv. The glycemic index compares the ↑ in blood sugar after the ingestion of simple sugars and complex carbohydrates with the ↑ that occurs after the absorption of.
2. Exercise: Exercise program must be individualized and built up slowly. Consider beginning with 15 min of low-impact aerobic exercise 3 ×/wk and increasing the frequency and duration to 30 to 45 min of moderate aerobic activity (50% to 70% of maximum age predicted heart rate) to 3 to 5 days/wk. In the absence of contraindications, resistance training 3 ×/wk should be encouraged.
3. Weight loss: to ideal body weight if the pt is overweight
• Maintain HbA1c <7%. HbA1c 7.5 or higher may be reasonable in elderly pts with limited life expectancy and ↑ risk of hypoglycemia.
• When the previous measures fail, oral hypoglycemic agents (Table 5-2) should be added to the regimen in type 2 DM. If renal function is not significantly impaired (creat < 1.3), metformin is the preferred initial hypoglycemic agent. GLP-1 agonists and dipeptidyl peptidase-4 inhibitions are preferred as additional oral hypoglycemics but cost is a limiting factor, especially in elderly patients.
• Insulin: indicated for all pts with type 1 DM and for pts with type 2 DM whose condition cannot be adequately controlled with diet and oral agents. Insulin Rx may be started with oral agents at 0.3 unit/kg, or as replacement, starting at 0.6 to 1 unit/kg. Table 5-3 describes commonly used types of insulin.
a. The risks of insulin Rx include weight gain, hypoglycemia, and in rare cases, allergic or cutaneous reactions.
b. Replacement insulin Rx should mimic nl release patterns.
i. 50% to 60% of daily insulin can be given as a long-acting insulin (NPH, ultralente, glargine, detemir) injected qd or bid.
ii. 40% to 50% can be short-acting (regular) or rapid-acting (lispro, aspart, glulisine) to cover mealtime carbohydrates and correct ↑ current glucose levels.
• Continuous subcutaneous insulin infusion (CSII, or insulin pump) provides better glycemic control than does conventional Rx. It should be considered for DM in childhood or adolescence and during pregnancy.
• The Diabetes Control and Complications Trial (DCCT) showed that intensive Rx for glucose control ↓ the development and progression of complications of type 1 DM. In this trial, the risks for retinopathy, nephropathy, and neuropathy were ↓ by 70%, 54%, and 64%, respectively.
• Low-dose aspirin (ASA; 81 mg/day): for primary prevention in diabetic pts with one additional CV risk factor, including age >40 yr, cigarette smoking, HTN, obesity, albuminuria, hyperlipidemia, and family hx of CAD
• Statins: DM >40 yr with ≥1 risk factor for CAD; LDL goal <100 mg/dL, <70 mg/dL if overt CAD
• BP control: SBP <130 DBP <80 mm Hg. Use ACEI to ↓ albuminuria and prevent CKD regardless of presence of HTN.
• Bariatric surgery: consider in adults with BMI >35 kg/m2 and type 2 diabetes
• Hypoglycemia Rx: conscious person → glucose tab or gel 15 to 20 g; unconscious → IM glucagon
• Neuropathy Rx: duloxetine, pregabalin, gabapentin
• Diabetic gastroparesis Rx: endoscopic injection of botulinum toxin into the pylorus and gastric electrical stimulation (using f electrodes placed laparoscopically in the muscle wall of the stomach antrum and connected to a neurostimulator)
• Nephropathy: ACEIs or ARBs (if intolerant to ACEIs)
• Glycemic control in hospitalized pts: Avoid intensive insulin Rx. The ACP recommends a target blood glucose level of 140 to 200 mg/dL if insulin Rx is used. Table 5-4 describes an insulin sliding scale.
1. Diabetic Ketoacidosis
Metabolic decompensation in diabetic pts usually precipitated by an infectious process (≤40% of cases). Poor compliance w/insulin Rx and severe medical illness (e.g., CVA, MI) are other common causes. Consider cocaine abuse in middle age DM w/multiple DKA admissions.
Diagnosis
PE
Evidence of dehydration (tachycardia, hypotension, dry mucous membranes, sunken eyeballs, poor skin turgor)
Clouding of mental status
Tachypnea w/air hunger (Kussmaul’s respiration)
Fruity breath odor (caused by acetone)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.
Lipemia retinalis in some pts
Possible evidence of precipitating factors (infected wound, pneumonia)
Abd tenderness in some ptsLabs
Glucose level is generally >250 mg/dL; urine and serum ketones (+) (usually 7-10 mmol/L).
ABGs reveal acidosis: arterial pH usually <7.30 w/Pco2 >40 mm Hg.
Serum electrolytes:• Serum bicarbonate is usually <18 mEq/L.
• Serum K+: may be ↓, nl, or ↑. There is always significant total body K+ depletion regardless of the K+ level.
• Serum Na+: usually ↓ (pseudohyponatremia) as a result of ↑↑ glucose, dehydration, and lipemia. Assume 1.6 mEq/L ↓ in extracellular Na+ for each 100 mg/dL↑ in glucose.
• Calculate the AG: AG = Na+ − (Cl− + HCO3−).
• In DKA, the AG is ↑ (generally >15); hyperchloremic metabolic acidosis may be present in unusual circumstances when both the GFR and the plasma volume are well maintained.
CBC w/diff, U/A, urine and blood cultures to r/o infectious precipitating factor
Serum Ca2+, Mg2+, and PO4-3; plasma PO4-3and Mg2+ levels may be significantly depressed and should be rechecked within 24 hr because they may ↓ further w/correction of DKA.
↑ BUN and Cr secondary to significant dehydration
Amylase, LFTs should be checked in pts w/abd pain.Imaging
CXR is helpful to r/o infectious process. The initial CXR may be nl if the pt has significant dehydration. Repeat CXR after 24 hr if pulmonary infection is strongly suspected.
Treatment
Fluid replacement (the usual deficit is 6-8 L), insulin Rx, electrolyte replacement
2. Hyperosmolar Non-Ketotic Coma, Honk
Definition
This is a state of extreme hyperglycemia, marked dehydration, serum hyperosmolarity, mental status changes, and absence of ketoacidosis.
Etiology
Infections, 20% to 25% (e.g., pneumonia, UTI, sepsis)
New or previously unrecognized diabetes (30%-50%)
Reduction or omission of diabetic medication
Stress (MI, CVA)
Drugs: diuretics (dehydration), phenytoin, diazoxide (impaired insulin secretion)Diagnosis
H&P
Evidence of extreme dehydration (poor skin turgor, sunken eyeballs, dry mucous membranes)
Neurologic defects (reversible hemiplegia, focal seizures)
Orthostatic hypotension, tachycardia
Evidence of precipitating factors (pneumonia, infected skin ulcer)
Coma (25% of pts), deliriumLabs
Hyperglycemia: serum glucose usually >600 mg/dL
Hyperosmolarity: serum osmolarity usually >340 mOsm/L
Serum Na+: may be ↓, nl, or ↑; if nl or ↑, the pt is severely dehydrated because glucose draws fluid from intracellular space = ↓ serum Na+; the corrected Na+ can be obtained by the serum Na+ concentration by ↑ 1.6 mEq/dL for every 100 mg/dL ↓ in the serum glucose level above nl.
Serum K+: may be ↓, nl, or ↑; regardless of the initial serum level, the total body deficit is approximately 5 to 15 mEq/kg.
Serum bicarbonate: usually >12 mEq/L (average is 17 mEq/L)
Arterial pH: usually >7.2 (average is 7.26). Both serum bicarbonate and arterial pH may be lower if lactic acidosis is present.
↑ BUN: Azotemia (prerenal) is usually present (BUN generally ranges from 60-90 mg/dL).
↓ PO4-3: hypophosphatemia (average deficit is 70-140 mM)
↓ Ca2+: hypocalcemia (average deficit is 50-100 mEq)
↓ Mg2+: hypomagnesemia (average deficit is 50-100 mEq)
CBC w/diff, U/A, blood and urine cultures should be performed to r/o infectious etiology.Treatment
Vigorous IV fluid replacement, electrolyte replacement, insulin Rx (see Fig. 5-1)B. Hypoglycemia
Definition
Hypoglycemia can be arbitrarily defined as a plasma glucose level <50 mg/dL. To establish the dx, the following 3 criteria are necessary:
Presence of sx• Adrenergic: sweating, anxiety, tremors, tachycardia, palpitations
• Neuroglycopenic: seizures, fatigue, syncope, headache, behavior changes, visual disturbances, hemiplegia
↓ Plasma glucose level in symptomatic pt
Etiology
Reactive hypoglycemia• Hypoglycemia usually occurs 2 to 4 hr after a meal rich in carbohydrates.
• These pts never have sx in the fasting state and rarely experience loss of consciousness secondary to their hypoglycemia.
• Pts who have had subtotal gastrectomy rapidly absorb carbohydrates. This causes an early plasma glucose level followed by a late insulin surge that reaches its peak when most of the glucose has been absorbed and that results in hypoglycemia.
• Pts with type 2 (non–insulin-dependent) diabetes can experience hypoglycemia 3 to 4 hr postprandially secondary to a delayed and prolonged second phase of insulin secretion.
• Congenital deficiencies of enzymes necessary for carbohydrate metabolism and functional (idiopathic) hypoglycemia are additional causes of reactive hypoglycemia.
Fasting hypoglycemia• Sx usually appear in the absence of food intake (at night or during early morning).
• Etiology: insulinoma, mesenchymal tumors that synthesize insulin-like hormones, adrenal failure, glycogen storage disorders, severe liver disease or renal disease
Iatrogenic or drug-induced: hypoglycemic drugs, excessive insulin replacement, factitious, ethanol-induced hypoglycemiaDiagnosis
When the plasma glucose level is ↓ (e.g., fasting state), the plasma insulin level should also be ↓. Any pt presenting w/fasting hypoglycemia of unexplained cause should have the following tests drawn during the hypoglycemic episode (Table 5-5):• Plasma glucose
• Plasma insulin level
• Plasma C-peptide
• Plasma and urine metabolites of sulfonylurea levels and meglitinides
Factitious hypoglycemia should be considered, especially if the pt has ready access to insulin or oral hypoglycemic agents (e.g., medical or paramedical personnel, family members who are diabetic or in the medical profession).
Pancreatic islet cell neoplasms (insulinomas) are usually small (<3 cm), single, insulin-producing adenomas. Measurement of inappropriately serum insulin levels despite ↓ plasma glucose level after prolonged fasting (24-72 ↑ hr) is pathognomonic of these neoplasms.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
Variable, depending on etiology of hypoglycemiaC. Anterior Pituitary Disorders
1. Hypopituitarism
Partial or complete loss of secretion of one or more pituitary hormones results from diseases of the hypothalamus or pituitary gland.
Etiology
Hypopituitarism is the result of destruction of pituitary cells caused by
Pituitary tumors• Macroadenomas >10 mm
• Microadenomas ≤10 mm
Pituitary apoplexy caused by hemorrhage or infarction of the pituitary gland
Pituitary radiation Rx
Empty sella syndrome w/enlargement of the sella turcica and flattening of the pituitary gland (from extension of the subarachnoid space and filling of CSF into the sella turcica)
Infiltrative disease including sarcoidosis, hemochromatosis, histiocytosis X, Wegener’s granulomatosis, and lymphocytic hypophysitis
Infection (TB, mycosis, and syphilis)
Head trauma
Internal carotid artery aneurysmDiagnosis
H&P
Sx are related to the lack of one or more hormones or mass effect.
Mass effect → headaches, visual field disturbances
Corticotropin deficiency• Fatigue and weakness
• Hypotension, hair loss
Thyrotropin deficiency• Fatigue and weakness, weight gain, cold intolerance, constipation
• Bradycardia, ↓ DTR, pretibial edema, hair loss
Gonadotropin deficiency• Loss of libido, erectile dysfunction, amenorrhea, hot flashes, dyspareunia, infertility
• Gynecomastia w/lack of hair growth and ↓ muscle mass
GH deficiency• Growth retardation in children
• Fatigue, hypoglycemia
• ↓ Muscle mass, obesity
Hyperprolactinemia• Galactorrhea
• Hypogonadism
Vasopressin deficiency• Polyuria, polydipsia
• Hypotension, dehydration
Baseline Labs
Corticotropin deficiency:• ↓ Serum AM cortisol level (<3 g/dL)
Thyrotropin deficiency:• TSH and free T4 measurements
• Primary hypothyroidism: ↑ TSH, ↓ free T4
• Secondary hypothyroidism: nl/↓ TSH, ↓ free T4
Gonadotropin deficiency:• FSH, LH, estrogen, and testosterone measurements
• In men ↓ testosterone levels, nl/↓ FSH and LH levels
• In premenopausal women w/amenorrhea, ↓ estrogen w/nl/↓ FSH and LH levels
GH deficiency:• ↓ Serum IGF-1
Provocative testing for pituitary insufficiency is summarized in Table 5-6.
Imaging
MRI of pituitaryTreatment
Hormone replacement Rx and surgery, irradiation, or medications in pts w/pituitary tumors
Acute situations such as adrenal crisis and myxedema coma are discussed separately.
Long-term Rx: lifelong and requires the following hormone replacement Rx:• ACTH deficiency: hydrocortisone 20 mg PO q AM and 10 mg PO q PM or prednisone 5 mg PO q AM and 2.5 mg PO q PM. Dexamethasone or prednisone is often preferred because of longer duration of action.
• LH and FSH deficiency:
• In men, testosterone replacement
• In women who are not interested in fertility, conjugated estrogen 0.3 to 1.25 mg/day and held the last 5 to 7 days of each month w/the addition of medroxyprogesterone 10 mg/day given during days 15 to 25 of the nl menstrual cycle. In those who have secondary hypogonadism and wish to become pregnant, pulsatile GnRH may be of benefit.
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 −
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