Steven W. Brose, D.O.Clinical Professor of Specialty Medicine, Ohio

University Heritage College of Osteopathic MedicineAssistant Professor, Case Western Reserve University

SCI Physician, Louis Stokes VAMC, Cleveland

Disclosures No financial conflicts of interest to disclose with this

work

Last year’s presentation (which formed the foundation for this presentation) was prepared by Dr. James K. Schmitt from Richmond, Virginia

Question writer for the ABPMR SCI subspecialty board examination but have not yet participated in a question writing cycle. I am a prior oral board examiner.

I am a chapter author in the next edition of Kirshblum& Lin SCI Medicine (Functional Electrical Stimulation)

Reference

Schmitt,J , Schroeder, D “Endocrine and Metabolic Consequences of Spinal Cord Injury” in Lin, VW edSPINAL CORD MEDICINE-Principles and Practice. 2010;278-290

Material is based primarily on this reference.

Survey of the Audience…Please raise your hand if you are planning to take the SCI medicine board examination soon

Effects On Autonomic Nervous System

Sympathetic fibers coming from T5-12 innervate the pancreas, adrenal medullar, and juxtaglomerular apparatus of the kidney – so injuries above T12 can have impact on these systems

Parasympathetic Nervous System : stimulates insulin secretion, while the sympathetic system inhibits it

Sympathetic Nervous System Sympathetic Nervous System Inhibits Insulin

Secretion Loss of sympathetic system is generally short lived –

occurs during spinal shock – usually recovers within weeks of injury

So In Acute SCI, Insulin and Aldosterone Tend To Be Higher – due to unopposed parasympathetic activity (?reverse autonomic dysreflexia of the autonomic system)

Sympathetic chain ganglion still functions below injury

Indirect Endocrine Effects Renal Failure (chronic UTIs, reflux etc) can result

in phosphate retention, hypocalcemia, and secondary hyperparathyroidism

Stress response: after illness or injury there can be impaired growth hormone secretion, reducing intrinsic stimuli for growth and maintenance of muscle mass. Also suppresses FSH and LH, which can result in lower testosterone and estrogen levels, and effect upon pituitary gland…

Metabolic syndrome: Denervation leads to muscle wasting and decreased activity with increasing bodyfat buildup, insulin resistance, hyperlipidemia, HTN

Pituitary Function No Direct SCI Effect On Pituitary gland, because

does not require an intact spinal cord injury…..…but 47% of SCI Has Concomitant TBI, which can result in pituitary injury. Acute stress response causes ACTH release,

stimulating cortisol production to maintain blood pressure: ADAPTIVE RESPONSE TO THE INJURY

Persons with tetraplegia may have LACK of ADH surge at night time, contributing to nocturnal urine production. ADH administration at night has been used

Pituitary Function, Continued Acute Hypopituitarism Caused by Trauma in SCI: Manifest

By Diabetes Insipidus (polyuria) and Adrenal Insufficiency; or can be due to renal tubule injury (lithium use)

Diagnosis of diabetes insipidus: patient passing large amounts of dilute urine which fails to concentrate with fluid restriction.

Treated by desmopressin intranasally 2.5-20 microgram doses, or intravenously.

SIADH Due To Lung Tumors, Pituitary Damage, Pneumonia and Other Infections

Diagnosis: Low Serum Sodium and Osmolality High Urine Sodium and Osmolality

Treatments: Fluid Restriction, Demeclocycline (causes nephrogenic diabetes insipidus)

Thyroid Disorders HyperthyroidismProblem: Can be difficult to diagnose in SCI: weight loss, anxiety, hyperthermia, hyperactive reflexes, tremors…

HypothyroidismAlso difficult to diagnose in SCI. Weight gain, hypothermia, constipation, delayed relaxation phase of deep tendon reflexes….

Treatment: Levothyroxine 0.05 to 0.2 mg per day (Start LOW and Go SLOW) – silent myocardial ischemia risk in tetraplegia

Effect of SCI On Thyroid Testing Sick euthyroid syndrome. Results in low T3 and

elevation of reverse T3.

Life threatening illnesses: proteins produced that displace T4 from binding site – low TSH, total T4 decreased. Low T4 correlates with poor prognosis in acute illness.

Study by Prakash found that in acute SCI, conversion of T4 into T3 is impaired: lowest T3 in acute tetraplegia, highest in acute paraplegia

Adrenal Insufficiency Most Commonly Due to Chronic Steroid Use Less Common Causes autoantibodies, or

infiltrative disorders such as cancer Manifest by hypotension, hyperkalemia,

hyponatremia, abdominal pain, Dx Low random cortisol, abnormal cortrosyn stim

test (Normal-basal 7 ug/ml and increases to 18 or higher after 0.25 mg of Cortrosyn IV or IM

Rx glucocorticoids Confounding factor: pheochromocytoma can

produce hypertension, tachycardia, headache, sweating…(looks like AD)

Autonomic Dysreflexia Vs Pheochromycytoma AD Intermittent HTN Usually Provoked by Visceral Stimulation Sweating Localized To Upper Body or Unilateral Bradycardia Vasodilation Above Level

Pheo More Chronic Rarely

Diffuse

Absent Absent

Diabetes Mellitus Fasting Serum Glucose Above 126 mg/dl Or Random Glucose Above 200 mg/dl Type I –Due to Pancreatic Destructionby antibodies or other causesType II –Due to Insulin Resistance and Genes

Over time Type 2 leads to beta cell exhaustion and insulin is required to maintain diabetic control

Oral Agents

Metformin 500-2000 mg/ day Pioglitazone 15-45 mg/day Glyburide 2.5-20 mg /day Glipizide 2.5-20 mg/day Repaglinide 1-4 mg with every meal Acarbose 25-150 mg per day

Exenatide and DPP-4 Inhibitors (gliptins)Type 2 Sodium-Glucose Transport Inhibitors

Insulin Therapy Basal Insulin Level-Glargine or NPH Divide Body Weight in Kg By 10 to Calculate

Beginning Dose Which Is Usually Given HS

Preprandial Insulin-Give One Unit of Lisproper 8 grams of CH Before Meals eg 7-8 Units per 60

grams of CH.

Insulin Preparations Type

Short ActingLisproAspartRegular

Intermediate ActingNPH

Long ActingGlargineDetemir

Duration (hrs)

3-43-6

6-8

10-16

>2418-24

Considerations In SCI Insulin Absorption is Higher In an Exercising

Extremity: Give Injection Below Level of SCI to avoid hypoglycemia from this effect

Complications of diabetes mellitus in SCI may be difficult to diagnosis: myocardial ischemia may be silent due to sensory denervation in tetraplegia; peripheral neuropathy may be silent (aside from diminishing reflexes), renal failure can be due to either diabetes or chronic pyelonephritis/refuls

ACE inhibitors protect the kidneys but may cause hypotension in tetraplegia due to presence of autonomic hypotension…use cautiously

Metabolic Syndrome Definition: collection of cardiovascular risk factors

that are due to insulin resistance Common in SCI: points out importance of

encouraging regular diet and exercise in SCI Diagnosis: presence of 3 out of 5 characteristics

(commonly occur in SCI) Abdominal obesity Elevated triglycerides Low HDL cholesterol Elevated blood pressure (increased in paraplegia) Elevated fasting glucose

Lipid disorders LDL goal depends on presence of other cardiovascular

risk factors Risk factors: male gender; age greater than 45;

hypertension; HDL cholesterol below 35; diabetes mellitus; history of smoking; family history of coronary disease

If

Brenes et al.

Calcium Homeostasis In SCI Bone Loss In Early SCI Parathyroid hormone is the primary hormone involved

in calcium homeostasis. Causes osteoclasts to release calcium from bone and increases renal phosphate exretion, stimulates conversion of 25-hydroxy Vitamin D to 1,25 form in kidney which casues calcium absorbtion by renal tubules.

People with SCI have decreased parathyroid hormone and 1,25 Vitamin D, increased serum phosphate and prolactin with normal calcium levels….degree of PTH suppression correlates with severity of neurologic injury

Baumann et al.

Hypercalcemia Occurs in immobilization in SCI: causes increased

osteoclast and decreased osteoclast activity, particularly in young patients

First line treatment is hydration with normal saline, increasing calcium excretion. Other options include intravenous pamidronate

Hypocalcemia Treated by intravenous calcium gluconate with

D5W Important to lower serum phosphate if it is

elevated before calcium is administered to avoid precipitation of calcium

Glucose stimulates insulin release, lowering serum phosphate

Hypoparathyroidism may result in chronic hypocalcemia – treat with calcium and vitamin D

Gonadal Function in Men Impaired Thermoregulation and TraumaDamage Testes Causing Primary HypogonadismFSH Elevation Indicates Impaired Seminiferous Tubule FunctionOpioids Cause Secondary Hypogonadism As Does Stress And Disease

Semen analysis: decreased number and motility of spermatozoa and abnormal morphology

KipreosEt al.

Androgen Replacement Replacement of Androgens In Hypogonadal Men

(Eg Testosterone Enanthate 200 mg IM q 3 Weeks or Topical Preparations).

Synthetic Androgens Such as Oxandralone Have Been Found to Improve Muscle Mass and Wound Healing in malnourished states, However They May Cause Liver Damage and Lower HDL CholesterolAndrogens Increase HemoglobinAndrogens Are Converted To Estrogens In Fat Which May contribute to ThrombosisAndrogens May Worsen Sleep Apnea

Gonadal Function In Women Less Affected In Women with SCI compared to men

Internal Location of Gonads Provides Protection

Estrogen Replacement Prevents Osteoporosis and Raises HDL, lowers LDL…However clinical studies show that estrogen increases thrombotic events, gall bladder disease and risk of endometrial cancer, therefore not recommended for prevention of coronary disease

Endocrine Aspects of SCI Steven W. Brose, D.O.

Clinical Professor of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine

Assistant Professor, Case Western Reserve University SCI Physician, Louis Stokes VAMC, Cleveland

Endocrine Aspects of SCI Steven W. Brose, D.O.

Clinical Professor of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine

Assistant Professor, Case Western Reserve University

Chief, VA SCI Center, Syracuse, New York

Endocrine Aspects of SCIDisclosuresReferenceSurvey of the Audience…Effects On Autonomic Nervous SystemSympathetic Nervous SystemIndirect Endocrine EffectsPituitary FunctionPituitary Function, ContinuedSIADH Thyroid DisordersEffect of SCI On Thyroid TestingAdrenal InsufficiencyAutonomic Dysreflexia Vs PheochromycytomaDiabetes MellitusOral Agents�Insulin TherapyInsulin PreparationsConsiderations In SCIMetabolic SyndromeLipid disordersSlide Number 22 Calcium Homeostasis In SCISlide Number 24HypercalcemiaHypocalcemiaGonadal Function in MenSlide Number 28Androgen ReplacementGonadal Function In WomenEndocrine Aspects of SCIEndocrine Aspects of SCI