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.


    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.


    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.

Thyroid Ups and Downs

Early in her husband’s presidency, first lady Barbara Bush began to lose weight. Her eyes became, in her own words “horrible and puffy” looking.” She had developed an autoimmune thyroid gland problem called Graves’ Disease. A few months later, the Bush‘s dog Millie came down with another autoimmune disease – lupus. The next spring, the president became ill with weight loss and a rapid, irregular heartbeat. Like Barbara he had Graves’ disease. Conspiracy theorists blamed Saddam Hussein for this outbreak of autoimmune disease in the White House, but thyroid experts saw nothing but coincidence. They admit, though, that they do not know what triggers antibody attacks against the thyroid gland, the most common cause of thyroid disease.

The many and varied symptoms of thyroid disease
Symptoms of thyroid disease most often involve effects of the hormones the gland makes. Thyroid hormone stokes the fire of metabolism, setting the rate of energy usage in every cell of the body and determining the basal metabolic rate (number of calories burned at complete rest).
Too much thyroid hormone causes hyperthyroidism; too little creates hypothyroidism. Extreme cases of either problem are easy to diagnose, but milder excess or deficiency states are much trickier and more common (an estimated 7-10% of adults have thyroid abnormalities). Hyperthyroid patients lose weight, become intolerant of warm environments and sweat profusely. Hair becomes thin and fine. The heart beats too fast and blood pressure rises, while muscles feel weak and hands shake. Sleep becomes elusive. On the hypothyroid end of the spectrum, lack of thyroid hormone banks the metabolic fires and drops the heat. Patients feel cold and become constipated. Incoming energy gets stored as fat; weight and cholesterol levels climb. Lethargy encroaches on daytime hours, and ambition and mental quickness decline. Both under and overactive glands can be enlarged and even visible as swellings just under the Adam’s apple.

The confirmation of the thyroid gland’s role in symptoms comes from blood tests that measure thyroid hormone levels. Extreme cases are easy to diagnose. Milder cases, with less impressive symptoms and “borderline” blood tests are trickier. Mild symptoms overlap many of life’s normal patterns that are unrelated to thyroid hormone: weight, blood pressure and cholesterol tend to go up with age; sedentary people frequently feel cold and constipated; women at menopause would sometimes like to abolish indoor heating, and physical and mental energy are always subject to lifestyle, happiness, and drug effects. The opinion of an endocrinologist is particularly helpful in interpreting borderline thyroid symptoms and lab values.
Thyroxin or T4 (with four iodine molecules) comes from the thyroid gland. Tri-iodothyronine (T3) comes from T4 when one iodine molecule is split off. Thyroid stimulating hormone (TSH), made in the pituitary gland, is like a thermostat that regulates how much T4 the thyroid gland makes. When T4 is too high, TSH goes down. When T4 is too low, TSH goes up. So hypothyroid patients have high TSH and low T4, and hyperthyroid patients have low TSH and high T4.
Symptoms suggesting hyperthyroidism, combined with high-normal T4 and T3 and low- normal TSH prompt further tests to look directly at the thyroid gland. Thyroid scans employ radioactive iodine and distinguish between glands that overproduce in all areas, ones that have nodules of overproduction, and enlarged glands that no longer make any hormone. Measurement of three different types of anti-thyroid antibodies further narrows the diagnosis.

The problems with the tests
Not all labs use the same ranges of normal values. Some rely on broad TSH ranges found in a random selection of apparently healthy people (0.32 -5.0 µIU/ml). Other labs use a much narrower range (.34-2.5µIU/ml) found in people who have been screened to rule out thyroid disease. So if you see a doctor who uses the first range and your TSH is 4.5, you might be told just to watch your weight, get better sleep, take a little blood pressure medicine and be rechecked in 6 months or a year. A doctor using the second might would give you a prescription for thyroid hormone. Treatment of hypothyroidism in these gray areas might normalize the blood tests without producing any clinically identifiable benefits. Nevertheless, it is wise to follow up on iffy test results because, over time, thyroid conditions may declare themselves further.

Autoimmune thyroid disease
Graves Disease and Hashimoto’s thyroiditis, caused by different types of antibodies, are the most common causes of thyroid problems and tend to run in families. In Graves ’ disease, the antibodies may also attack eye muscles and make them swell, producing the characteristic bulging eyes that Barbara Bush complained about. Graves disease most often begins with a hyperthyroid state that requires treatment to suppress overproduction of thyroid hormone or to obliterate the gland by radiation, producing hypothyroidism that requires treatment; sometimes Graves’ improves on its own but then goes on to hypothyroidism. Hashimoto’s disease most commonly bypasses the clinical hyperthyroid phase altogether and is the most common cause of hypothyroidism.

Iodine deficiency
Lack of dietary iodine once caused many cases of hypothyroidism. The word cretin (slang for dunce, idiot) originated in a mountainous French region where iodine deficient soil and lack of iodine-rich seafood resulted in a high incidence of mental and physical retardation from hypothyroidism in babies. Thyroid hormone and the dietary iodine required to make it are critical for normal growth and development, especially of the brain. In modern societies babies are screened and treated for hypothyroidism, and iodized salt makes this essential element easily available so this once frequent deficiency is much less common.

Oral, synthetic versions of T3 and T4, or “natural” versions made from batches of pig thyroid glands make failing thyroid glands easily treatable. Synthetic versions are easier to regulate than are the natural ones. Finding the proper dose to return the blood tests to the normal range is often much easier than finding the dose and timing of pills that improves symptoms. The latter process is an inexact science that sometimes results in too much hormone effect.
Overactive glands are treated with medicines that shut them down, sometimes with radioactive iodine that kills the glandular cells and sometimes with surgery to remove the entire gland. The latter two treatments always produce hypothyroidism which then requires treatment with replacement hormones.
One study on thyroid disease prevalence estimates that there are 13,000,000 Americans with undiagnosed thyroid problems. Thyroid tests are now part of routine blood work, more problems will be caught and treated earlier, and more will be learned about triggers for autoimmune thyroid problems – eventually putting at least one conspiracy theory to rest.

Notes on less Common Thyroid Conditions

Lumps in the thyroid: These are common and most are benign nodules or cysts; sometimes they produce thyroid hormone and cause hyperthyroidism.

Viral thyroiditis (also known as sub-acute thyroiditis): self-limited illness with several weeks of hyperthyroidism, followed by several weeks of hypothyroidism, and then recovery of normal function.

Thyroid cancer: Uncommon. Rarely produces thyroid hormone so usually the diagnosis results from evaluation of lump in the neck or hoarseness; results from radiation exposure – as once was the practice for treating acne.

Pituitary Gland Tumors: Pituitary failure to produce TSH causes hypothyroidism; very rarely the pituitary overproduces TSH and causes hyperthyroidism.

Dietary Hyperthyroidism: At least one outbreak of hyperthyroidism came from meat contaminated with animal thyroid glands. Another rare cause is sudden, excessive iodine supplementation in a patient with underlying thyroid disease .

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