Posts tagged:Cushing’s Disease

The Master Gland and its Tumors

“When you hear hoof beats think of horses before zebras.”
Adage familiar to most doctors, reminding them that most symptoms come from common problems. Author unknown.

Pituitary gland tumors are common, often found as unsuspected abnormalities in brain scans and in autopsies, and counted as the most common “brain tumors” removed by neurosurgeons. Technically though, the most common pituitary tumors – the horses – are not brain tumors, but gland tumors called adenomas, usually benign and eminently treatable. While more dangerous tumors arising from nearby parts of the brain or skull may closely mimic pituitary adenomas, they are rare – the zebras of pituitary problems. This column is about the horses and for simplicity will refer to pituitary adenomas as pituitary tumors.

What and where is the pituitary gland?

    The pituitary gland hangs like a little globe from the base of the brain. The back half of the gland is neural tissue, connected to the deepest regions of the brain above. The front half is glandular tissue, which, like other glands, makes hormones, secretes them directly into the blood, sends them out to perform many functions in other parts of the body and is prone to adenoma formation as life goes on.

Types of pituitary tumors

    Pituitary tumors which are “non-functioning,” i.e. producing no hormones, may never cause symptoms. Larger tumors or those that produce hormones typically come to attention in midlife, more often in women than men because female reproductive cycles is exquisitely sensitive to hormonal variations. Small, unsuspected tumors turn up in about 10% of MRI scans of the head done for unrelated reasons like sinus disease or head trauma, and in 20-25% of autopsies.

     The factors which determine whether or not a pituitary tumor produces symptoms and requires treatment include its size, its ability to produce hormones of its own, and the degree to which it compresses and damages normal pituitary gland tissue and other surrounding structures. Damage to the normal parts of the gland that diminishes production of pituitary hormones is a condition called pituitary insufficiency. Production of a hormone by a pituitary tumor is called pituitary hypersecretion, which causes predictable signs and symptoms related to the effects of hormonal overdose on the given hormone’s target organs and tissues. Pressure on nearby brain structures by a large pituitary tumor is a phenomenon called tumor mass effect.

Pituitary insufficiency

    Some pituitary hormones such as thyroid stimulating hormone (TSH) prompt other glands to produce their hormones. Other pituitary hormones work directly on many body tissues. Growth hormone, for instance, affects all tissues in the body, controlling growth in early life and many aspects of tissue repair later. Still others control menstrual function, ovulation, and production of sperm, testosterone and breast milk. The rear half of the pituitary gland, which arises from the brain, makes one hormone that helps concentrate urine and another, called oxytocin which stimulates uterine contraction during labor, and has recently been suspected to play a role in some moods and behaviors.

When insufficiency becomes failure

    If a pituitary tumor compresses the normal parts of the gland, causing it to fail, wide-ranging symptoms such as fatigue, headache, weakness, abnormal menstrual cycles, decreased libido, decreasing muscle mass and body hair, weight loss or weight gain and mood alterations may appear long in advance of a correct diagnosis. These are all symptoms which might easily be passed off as lifestyle problems, nutritional deficiencies and aging.

Pituitary Hypersecretion 

    If pituitary tumors are functional, i.e. producing hormones,  symptoms come from excessive hormonal effects on the body. For instance, growth hormone (GH) and the adrenal gland stimulating hormone ACTH are the most common tumor-produced hormones. In someone still growing, too much growth hormone produces a giant – someone whose proportions are normal, but who far exceeds the normal range of sizes. Think Andre the Giant. Once growth ceases, overabundant growth hormone still causes overgrowth in certain bones and tissues, especially the jaw, hands and feet, the nose, heart and tongue, and the heel pads. This condition is called acromegaly.

    ACTH overproduction produces Cushing’s disease, named after Harvey Cushing, the father of neurosurgery in the US, one of the first to try surgically removing a pituitary tumor. Weight increases around the trunk and in the face and neck; muscles and tendons weaken and atrophy. Bones lose calcium. Eyes bulge. Skin bruises and thins. Blood pressure goes up.

Tumor Mass Effect 

    A large tumor in the pituitary may compress not only the normal gland around it but also the surrounding structures in the brain and skull. The gland sits right below the junction of the optic nerves carrying visual information from the eyes to the brain, and in between the bones where the nerves that control eye movements enter the orbits. In addition, the large veins which drain blood from the brain travel beside the pituitary on their way out of the skull. The optic nerves fibers that carry vision from the sides of the visual field are most vulnerable to pressure, which impairs sight on both sides of the patient’s field of vision. Pressure on the nerves to the eye muscles causes double vision. Headache, eye pain, or eye redness comes from mass effect on the large veins coursing beside an enlarged pituitary. Very large tumors may affect the deep brain structures above, resulting in a host of emotional symptoms or seizures.

Diagnosis 

    Symptoms which suggest pituitary gland insufficiency, hypersecretion or tumor mass effect warrant hormonal testing, an ophthalmologist’s examination of the visual fields, and imaging studies of the base of the brain. Tumors found incidentally on scans done for other reasons should prompt a good medical history and physical examination, and possibly some hormonal testing to evaluate the functional status of the tumor.

Treatment 

    Surgical removal of the pituitary tumor is the treatment for functional tumors or those that damage surrounding structures. After surgery, patients might require either temporary or permanent supplementation with pituitary hormones. On rare occasion, abrupt pituitary failure called pituitary apoplexy is the result of a pituitary tumor bleeding. this is a medical emergency, requiring  emergency surgery with meticulous attention to fluid balance and blood pressure because of failure of the hormones that modulate those functions. Non-functioning, small pituitary tumors call for regular follow-up imaging to monitor the tumor size – and should not carry the fearsome designation of brain tumor. They are horses, not zebras.

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Posted by medical plaintalk

Physician turned medical writer.

The Problem with Stress: No Fighting or Fleeing

…grant me the serenity
to accept the things I cannot change;
courage to change the things I can;
and wisdom to know the difference….

from The Serenity Prayer, by Reinhold Niebuhr

     Picture an early human moving through the quiet forest, intent on the prey he’s tracking. His pace is steady and his mind focused. Suddenly a bear bursts through the trees.  Emotional centers in primitive parts  the hunter’s brain fire off  threat messages which race through the sympathetic nervous system to his adrenal glands—little thumb size organs buried in fat and sitting on top of the kidneys.  Almost instantly, each gland responds with a burst of adrenalin from its central core, the adrenal medulla. Danger also prompts his pituitary gland to pour out a big dose of adrenocorticotropin (ACTH), a hormone that speeds through the blood to the adrenal cortex, the outer 80% of the gland. In response, the gland releases cortisol, a powerful glucocorticoid hormone involved in energy regulation.

The hunter’s pulse and blood pressure shoot up.  His airways dilate and he breathes faster.  His vision narrows and sharpens. Anticipating action, his muscles and liver free glucose and fat from storage.  By the time he races to a nearby tree to haul himself to safety,  the cascade of neural and hormonal events has shifted his metabolism from quiet homeostasis (maintenance of normal function) to an active state designed for fleeing….or for fighting if the bear climbs too.  When the bear loses interest and wanders away, our early man’s activated physiology reverts to routine functioning. He climbs down, resumes his methodical hunt and cooks his game over an open fire. From sundown to sunup, he sleeps.

Now consider a modern man as he rushes through his urban environment. He becomes anxious and then angry when his train is late. As he hails a cab he narrowly misses being hit by an oncoming car. Horns blare.  He flops down in the back seat of the cab, fumbling for his ringing cell phone, only to hear that his boss is angry because he is late.  Inside our overweight modern man’s body,  early hunter physiology whips his adrenal glands into action – over and over and over. But he does not get to fight or flee. Worse yet, the threats in his environment do not lose interest and wander away.  He will be on edge all day, and perhaps late into the night.  After a few drinks, a few smokes, a fast food meal and some paperwork, he falls asleep in front of the TV, finally stumbling into bed in the wee hours of the morning. By 6AM he’s starting over, sleep-deprived.

The adrenal gland connection

In both early and modern humans, the brain-adrenal connection is heavily influenced by environment, genetic makeup, lifestyle and memory of previous experiences. We learn fear and make habits of emotional responses. While animal research can’t take into account human mental components of stress, it has provided useful physical insights, especially about the adrenal connection to chronic stress. Experiments in “rat micro-societies” refined the fight-or-flight concept and divided it into aggressive defense and passive defeat responses, an important distinction because each type activates different parts of the adrenal glands.

Rats responded with passive defeat when a task like pushing a lever sometimes produced food, sometimes didn’t, sometimes in one place, sometimes in another, and sometimes not at all. The consequences of the rats’ actions were uncontrollable and feedback didn’t help them learn.  In these circumstances the adrenal cortex overproduced cortisol.  If you think the passive defeat experiments resemble average life, then you’ll guess, correctly, that chronic stress in people might also trigger elevated cortisol levels.

Aggressive defense responses to the rat equivalent of being mugged, in contrast, activated primarily the adrenal medulla, which takes charge of the immediate activity necessary to survive a threat by producing an adrenalin rush – a burst of the hormones epinephrine and norepinephrine. In states of fear and/or anger, we experience this rush as rapid pulse, elevated blood pressure, increased breathing rate, flushing, pallor and dry mouth.

In our early hunter these adrenal responses are sequential. First comes the adrenalin rush which helps him survive.  Following just behind,  the adrenal cortex ramps up hormone production to help restore normality–to restock energy supplies, dampen pain and divert resources from routine activities.The system is designed for short bursts of danger, not for chronic immersion in mental stress.

The metabolic syndrome connection

Beginning in 2002, researchers began to correlate adrenal hormone abnormalities with the modern plague of the metabolic syndrome—abdominal obesity, insulin resistance, diabetes and high blood pressure, all reliable side effects of exposure to excessive cortisol, whether it comes from drugs like prednisone or from  pituitary or adrenal gland diseases. (See note on Cushing’s disease below).  No one thinks cortisol and stress are wholly responsible for our metabolic epidemic, but many hope that the stress connection will help lead to a solution.

Counteracting the stress response

Stress researchers uniformly conclude that short of retreating from the world, the only major defense that counteracts the effects of stress is regular physical activity which dissipates some of the energy mobilized for action.  The best results come from superimposing physical activity on a lifestyle that accommodates enduring human needs: sufficient sleep, diet suitable for an ancient physiology, good social network and engagement in focused activity that has personal value. Even then, coping strategies are necessary.

A Note on Cushing’s Disease

    The most dramatic demonstration of the results of too much cortisol occurs in patients with Cushing’s disease, usually caused by a pituitary gland tumor which overstimulates  the adrenal cortex.  In these patients, muscles are thin and weak, and excess weight is concentrated in the trunk and face and neck.  Patients have red, jowly faces and skin scored by purplish stretch marks and poorly healed wounds. Bones are robbed of calcium and osteoporotic upper backs round forward under the characteristic “buffalo hump” of fat.  The adrenal cortex hormones also have weak male hormone effects causing male pattern baldness and excess facial hair in women.  The immune system is weakened and health is further damaged by diabetes, high blood pressure and heart disease.

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Physician turned medical writer.
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