Endocrinology and Sports
J. Andrew McMahon
William W. Dexter
The endocrine system is a complex framework of glands and hormones that takes input and provides feedback to the hypothalamic-pituitary axis. The hormones are often ubiquitous and ultimately govern many key physiologic functions, such as metabolism, growth, and muscle function. Hormones are responsible for the machinery that allows us to exercise, and when deficient, provides a management challenge to both the athlete and the sports medicine physician. This chapter will review some of the key components of the endocrine system and the implications of disease of this system in sports.
PANCREATIC HORMONES
Insulin and glucagon are secreted by the islet cells in the pancreas. Glucagon is a catabolic hormone secreted as a counter balance to insulin through its stimulation of gluconeogenesis.
Insulin is an anabolic hormone that regulates glucose channels and insulin receptors, stimulates protein and glycogen synthesis, and generally inhibits catabolism. When it is absent, lipolysis produces fatty acids and ketones as the primary fuel source, resulting in a metabolic acidosis. Insulin is also involved in development through its numerous interactions with other mediators of growth-like growth hormone (GH) and insulin-like growth factor-1 (IGF-1) (20).
During exercise, insulin levels decrease while glucagon and catecholamines drive hepatic glycogenolysis and free fatty acid production to provide glucose to stressed cells. In this state, active muscles use glucose through insulin-independent means and potentiate the action of residual insulin through adaptations in the affinity for and quantity of insulin receptors.
After exercise, insulin production and sensitivity are increased in response to elevated blood sugars. Insulin drives replenishment of glycogen and protein stores and downregulates counterregulatory hormones.
Diabetes and exercise
Because insulin is administered exogenously in diabetics, this cascade relies heavily on proper management. Insulin in excess prior to exercise inhibits catecholamines, suppressing the liver’s ability to mobilize fuel while muscles continue to use circulating glucose. Hypoglycemia, with blood sugars < 70 mg · dL−1, ensues.
Hypoglycemic emergencies arise as the counterregulatory hormones are inhibited by the exogenous insulin. Following exercise, enhanced glucose uptake and insulin sensitivity predisposes the insulin-dependent diabetic to hypoglycemia for as much as 12-24 hours.
Pallor, diaphoresis, confusion, headache, shakiness, irritability, and a change in mental status are common presentations and may progress to syncope, seizure, or coma if left untreated.
Athletes with long-standing diabetes have a blunted stress response and may not exhibit these warning signs, which are the result of sympathetic activation. Fatigue, hunger, and irritability may be the only clues (22).
Treatment, if alert, is oral replacement with 15 g of glucose.
□ Repeat blood sugar every 15 minutes until euglycemic.
□ If obtunded, administer glucagon 1 mg intramuscularly (IM)/subcutaneously (SC) if > 100 lb or 0.5 mg if < 100 lb.
Glucagon has a short half-life and should be continuously supplemented with additional carbohydrates until sugars normalize (7).
Hyperglycemia can also be problematic for athletes when insufficient insulin is present during exercise. When control is poor prior to exercise, athletes may have high blood glucose and subsequent polyuria resulting in dehydration. Without insulin’s inhibitory effect on lipolysis, ketogenesis contributes to the deteriorating metabolic state.
Counterregulatory hormones are normally active in the stressed state but in this setting, will contribute detrimentally to the hyperglycemia. Diabetic ketoacidosis may be the end result. These athletes need urgent supplemental insulin and hydration.
Therapeutic use exemption (TUE)
No TUE is needed for insulin.
Return to play
Athletes with routine hypoglycemia can return to play when repeat blood sugars have stabilized. Blood sugars in excess of 250 mg · dL−1 or ketonuria is a relative contraindication to play. Athletes with sugars between 180 and 249 mg · dL−1 should be monitored closely but can continue to play.
PARTICIPATION GUIDELINES
Preseason
Assess athlete’s disease literacy.
□ Nutrition, carbohydrate counting
□ Ability to monitor blood sugars with appropriate frequency
□ Recognizes the symptoms of hypoglycemia and hyperglycemia
□ Knows how to treat diabetic emergencies, sick day plan
□ Medical alert bracelet
Screen for long-term complications of diabetes.
□ Recent hemoglobin A1c, blood pressure, lipid profile, creatinine, microalbumin
□ Screen for peripheral neuropathy, foot care education
□ Screen for retinopathy, if present, no heavy lifting
□ Consider screening for coronary artery disease
□ Graded exercise testing if older than 35 or 25 with > 15 years of diabetes
Create plan with sports medicine staff for diabetic emergencies.
Athlete should experiment in preseason with insulin regimens.
□ Start season conditioning to minimize changes in insulin needs that develop with fitness.
□ Experiment with injection site and effects of exercise and climate on absorption (38).
Before exercise
Estimate intensity, duration, and energy demand of event.
Reduce SC insulin based on intensity and duration of exercise.
□ Reduce premeal insulin by 20%-75%.
□ Reduce by 70%-80% if > 90 minutes in duration (38).
Insulin pump users should reduce basal rate by 50% 1 hour prior to sport.
□ May remove pump for up to 1 hour for sport, especially water or contact sports
□ Frequent glucose checks
□ Contingency plan for extended events (36)
Check blood sugars prior to exercise.
□ If blood glucose < 100 mg · dL−1, ingest 15 g of carbohydrate. Wait 15 minutes, and recheck blood sugar. Repeat as needed.
□ If blood glucose is between 180 and 249 mg · dL−1, increase frequency of blood sugar checks. Hold carbohydrate intake pending clinical course.
□ If blood glucose > 250 mg · dL−1, postpone exercise, measure urine ketone, and administer insulin.
During exercise
Add 15 g of carbohydrate for the first 30-60 minutes of exercise.
□ During events of longer duration, 30-60 g · h−1 carbohydrate should be ingested every 15-30 minutes.
Hydration
Monitor glucose levels at least hourly.
Postexercise
Meal within 30 minutes of activity and increased caloric intake for 12-24 hours after activity
Continued blood glucose surveillance, especially overnight
□ Watch for late-onset hypoglycemia.
□ Adjust insulin as needed.
Proper foot care
Hydration
THE ADRENAL GLAND
Adrenal Cortex
Adrenocorticotropin (ACTH), synthesized in the anterior pituitary, is secreted under control of corticotropin-releasing factor (CRF) and vasopressin. ACTH stimulates the adrenal glands to secrete glucocorticoids, mineralocorticoids, and weak androgens.
Glucocorticoids provide negative feedback to the hypothalamus when steroid levels are adequate, downregulating the axis.
Superficially, the zona glomerulosa produces mineralocorticoids (e.g., aldosterone). Mineralocorticoids help maintain blood volume by governing a sodium channel in the kidney under direction of the renin-angiotensin system and in response to fluctuations in potassium and blood pressure (39).
In the zona fasciculata, glucocorticoids (e.g., cortisol) are produced diurnally, with the highest concentrations secreted in the morning. The key functions of cortisol are to increase blood sugar through gluconeogenesis and glycolysis. Cortisol is a potent anti-inflammatory, decreases bone formation, strengthens cardiac muscle contractions, and causes water retention. Glucocorticoids are secreted in response to stress and hypoglycemia under direction of ACTH and catecholamines (39).
The deepest layer is the zona reticularis where weak androgens are produced. They are secreted with cortisol in response to stress and in a diurnal fashion. Please refer to the section on androgens for more details (39).
Adrenal Insufficiency
Insufficiency results when the adrenal glands, or the hypothalamic-pituitary axis, fail to produce steroids. Patients present with weakness, nausea, abdominal pain, or hypovolemia with orthostatic hypotension. Myalgias and paralysis secondary to hyperkalemia are not uncommon (25).
Diagnosis is suggested by hypoglycemia, hyponatremia, and hyperkalemia on routine fasting metabolic profile.
Cortisol and ACTH levels are a reasonable first step in diagnosis.
A fasting morning basal cortisol level < 3 µg · dL−1 is diagnostic.
The diagnosis is unlikely in an otherwise healthy individual with a level > 10 µg · dL−1 (25).
Treatment includes hydrocortisone (25-30 mg orally divided 3 times a day).
Fludrocortisone (0.1-0.2 mg every day) may be needed for additional mineralocorticoid activity.
Long-acting prednisone or dexamethasone may also be used (25).
Acute Adrenal Crisis
In those treated with exogenous steroids, an acute adrenal crisis may be precipitated by extreme stresses (surgery, infection, dehydration) or rapid withdrawal of long-term glucocorticoid therapy. Chronic prednisone administration results in corticotrophic cell atrophy and a subsequent inability to sustain the adrenal axis when the exogenous source is removed.
These individuals may present with shock, an “acute” abdomen, or high fever, or be comatose.
Normal exercise does not require stress doses of corticosteroids, but a fracture, moderate blood loss, or vomiting may precipitate an emergency.
Treatment includes 100 mg of injectable Solu-Cortef or 4 mg of dexamethasone.
Medication should be available at all times.
The athlete and sports medicine staff should be educated about how and when to use these rescue medications.
Attention to blood glucose levels and volume resuscitation with normal saline should be a priority.
Athletes with hypotension or hypoglycemia need to be transferred urgently to the nearest medical facility for volume resuscitation, intravenous steroids, and close monitoring of vitals and electrolytes (25).
TUE
For primary adrenal insufficiency, a TUE is granted for a term of 4 years (and often lifetime).
It is subject to yearly review by an endocrinologist.
A plan for adrenal crisis in times of high stress should be integrated into the TUE.
The athlete should report use of stress doses on the doping control form at time of testing.
A TUE for functional adrenal insufficiency resulting from glucocorticoid withdrawal can be granted for a period of 4-12 weeks.
Given the controversy surrounding the efficacy of and need for dehydroepiandrosterone (DHEA) supplementation, an independent expert should consulted (40).
Return to play
With adequate therapy and a TUE, there are no restrictions.
Adrenal Medulla
The adrenal medulla is a collection of postganglionic neurons under direct control of the central nervous system through autonomic preganglionic fibers. The medulla secretes catecholamines into the blood under direct stimulation of the autonomic nervous system in response to stress and exercise.
Catecholamines, which include norepinephrine and epinephrine, act at adrenergic receptors located throughout the body, activating the sympathetic division of the nervous system. They increase heart rate, cardiac output, and arterial pressure through the α-adrenergic receptors. Catecholamines also cause bronchodilation, vasodilatation, and mydriasis.
Ephedra alkaloids are weak sympathomimetic agents with actions similar to epinephrine. They are perceived as agents that improve competitiveness and focus and reduce tiredness. There are currently no data supporting the ergogenic benefit of ephedra alkaloids for power, endurance, strength, or speed. High doses of the compound can cause anxiety, delirium, irritability, aggression, and convulsions, although the most dangerous side effects are hypertension and tachyarrhythmia (3).
TUE
Ephedrine and stimulants, in general, are banned during competition. There is no TUE available.
There are a number of other agents acting on the adrenergic axis that are prohibited by the World Anti-Doping Agency (WADA); please refer to a current prohibited substances list for details.
THYROID HORMONE
Thyroid hormone (TH), produced by the thyroid gland under direction of the hypothalamic-pituitary axis, is secreted in response to elevated thyroid-stimulating hormone (TSH) when TH levels are low. When there is adequate hormone, negative feedback shuts down the axis.
TH helps govern fat mobilization, gluconeogenesis, and glycogenolysis and plays a key role in physical and neurologic development. It is responsible for maintaining body temperature through complex thermogenic mechanisms (15).
TH upregulates β-adrenergic receptors, resulting in an increased sensitivity to circulating catecholamine and has multiple responsibilities in muscle function. TSH and thyroxine (T4) have been shown to increase proportionally with exercise and, when preserved within normal physiologic parameters, appear to improve muscle efficiency with exercise and play a key role in physical and metabolic function (15).
Hypothyroidism
Manifestations are that of a slowed metabolic state that includes fatigue, slowed movement, cold intolerance, constipation, weight gain, delayed relaxation of deep tendon reflexes, and bradycardia.
In athletes, however, the complaint may be as simple as a decrease in performance or fatigue. This is a challenging and infrequent diagnosis in young athletes. In a 2007 study of 50 athletes with fatigue, only 6% were found to have abnormal thyroid function assays (8).
Cakir et al. (4) noted that 30%-80% of patients with hypothyroidism present with muscular complaints, including cramps, weakness, stiffness, and poor exercise tolerance.
Exercise intolerance is likely a result of mitochondrial dysfunction and loss of β-adrenergic receptors affecting many metabolic pathways that supply active muscles.
In extreme cases, this may cause rhabdomyolysis or a polymyositis-like weakness (4).
Carpal tunnel syndrome is also a common manifestation (4).
Function of the cardiovascular system is greatly affected by hypothyroidism. Both systolic function and diastolic function are reduced, and the relaxation of vascular smooth muscles is impaired, increasing systemic vascular resistance (16).Related posts:
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