Youthful, tanned, slim, sporty – if you look at old photos of John F. Kennedy, he looks perfectly healthy, the epitome of the dynamic statesman. But despite his vital appearance, Kennedy was seriously ill when he moved into the White House in 1961 as the 35th US President. At times he took eight medications a day.
Today it is proven that he suffered from Addison’s disease. One of the symptoms: the brown discoloration of the skin. The disease, named after its discoverer, the English doctor Thomas Addison, is based on a failure of the adrenal glands, two small glands that produce a large number of important hormones. Doctors today speak of adrenal hypofunction or insufficiency.
“In the last ten years we have made great progress in understanding adrenal diseases,” explains Martin Reincke, Director of the Medical Clinic and Polyclinic IV at the LMU Munich. Treatments that are as tailor-made as possible for patients – researchers and doctors are getting closer to this goal. Nevertheless, there is a need to catch up, according to Reincke.
Diseases of the adrenal glands are often only diagnosed years later. The consequences – for example in terms of performance and mental health – are sometimes far-reaching. New tests should help to track down hormone disorders more quickly. Experts are increasingly focusing on the quality of life of those affected. “So far, it has often not been optimal,” says Reincke.
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At first glance, the adrenal glands look like appendages to the kidneys – the three-pronged glands sit like little caps on the detoxification organs. They do their job in secret, but their impact is enormous.
The adrenal glands influence electrolyte balance, circulatory function, sugar, fat and protein metabolism, the immune system and bone metabolism. “We commonly associate coping with stress with the brain,” says the expert. “But the brain wouldn’t be able to deal with stress if it weren’t for the adrenal glands, which are the master organ that intervenes in a modulating manner.”
In stressful situations – including illnesses or infections – the endocrine glands are important: They produce the messenger substances cortisol and adrenaline as needed and thus ensure that the body mobilizes enough energy in the form of fat and blood sugar to overcome the crisis. Hormone secretion is partly controlled by the pituitary gland (hypophysis) with the help of hormonal messengers.
The hypothalamus, pituitary and adrenal glands are the pillars of a stress-activated hormonal axis. The control circuit uses several messenger substances to control the release of the hormone cortisol, which the body can use to cope better with crises
Each adrenal gland weighs only twelve grams, but there are basically four different organs in the two lightweights. “Each of the four layers that make up an adrenal gland is highly specialized and has its own function,” says expert Reincke.
“Nevertheless, the layers interact with each other.” The salt hormone aldosterone is formed in the outermost layer. It regulates the salt water balance and influences blood pressure. The gland produces the stress hormone cortisol in the middle layer, and special androgens, male hormones, in the inner layer.
The adrenal medulla in the center produces the alarm hormone adrenaline. If the finely tuned hormone factory becomes unbalanced, this can lead to far-reaching metabolic disorders.
Each adrenal gland is divided into medulla and cortex. Different hormones are produced in its four layers, which affect different organs.
The adrenal cortex has three layers and produces over 40 hormones. The most important are aldosterone, cortisol and androgens. Adrenaline is produced in the adrenal medulla. Adrenocorticotropic hormone (ACTH) is produced in the pituitary gland and released into the blood. It stimulates the cells in the adrenal gland to produce cortisol. Hormones from the hypothalamus and adrenal glands regulate ACTH levels
Fatigue, sluggishness, low blood pressure, loss of appetite, nausea, weight loss—many symptoms of adrenal hypofunction like Kennedy’s are nonspecific. “You quickly blame it on stress and overwork,” says Stefanie Hahner, deputy head of endocrinology at the University Hospital in Würzburg.
It is more common for psychiatric patients to be referred to hormone specialists who had previously been treated for suspected anorexia or depression. A brown discoloration of the skin is a more specific indication of the disease. “Sometimes those affected look as if they have come from vacation, even though they are doing really badly,” says Hahner.
Up to 80 percent of the main reasons for the lack of performance and function of the adrenal glands are autoimmune diseases. Tumors or infectious diseases such as tuberculosis and AIDS can also be the reason. Depending on the cause, too little cortisol and/or too little aldosterone is formed as a result. Since cortisol is essential for survival, the deficit must be compensated for by appropriate hormone replacement therapy – usually with hydrocortisone.
Studies at the University of Würzburg have shown that, in the long term, the ability of many patients to perform is limited despite hormone replacement therapy. “Unfortunately, we are not as good as nature, with its perfect daily rhythms, to enable differentiated and individually adapted hormone substitution,” says the expert. “That’s one of our big goals.”
In the vast majority of cases, adrenal insufficiency is insidious. However, it can also occur acutely and become noticeable with a drop in blood pressure, shock or diarrhea with vomiting. So-called adrenal crises occur when the body’s current need for cortisol is higher than replacement therapy can meet. “This is a life-threatening condition, an emergency,” emphasizes hormone expert Hahner.
A simple therapy helps in acute care: cortisol as an infusion or injection. “We train patients and relatives in a similar way to diabetics, so that they can assess situations themselves.”
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High blood pressure, a widespread disease, is caused more frequently than previously thought by a disorder of the adrenal glands. “Around 13 percent of all hypertension diseases are based on the so-called Conn syndrome alone, which affects 2.6 million people in Germany,” says Stephan Petersenn, a specialist in adrenal diseases from Hamburg and spokesman for the German Society for Endocrinology.
In this condition, the salt hormone aldosterone has lost the control of other hormones. The adrenal glands constantly and uncontrollably release too much aldosterone – blood pressure rises. In many cases, a mostly benign tumor of the adrenal cortex (Conn’s adenoma) causes the metabolic disorders.
According to studies, an average of ten years pass between the initial diagnosis of high blood pressure and the diagnosis of Conn syndrome. Only one percent of patients with unexplained high blood pressure are examined for the presence of the syndrome – the guidelines recommend a rate of 50 percent.
“This leads to a massive underdiagnosis,” says expert Reincke. Fatal, since the high blood pressure in Conn syndrome leads to a heart attack, stroke or heart failure five to ten times more often than in other hypertensive diseases.
One reason is the lack of effectiveness of the usual medication. “Blood pressure is difficult to adjust, there are patients who take six or eight antihypertensive drugs,” says researcher Reincke. “If three drugs are not effective enough, you should test for a hormonal disorder.”
Because the disease can often even be cured by surgery. If there is a small lump on one of the adrenal glands that stimulates hormone production, it can be removed using the keyhole technique.
More often, however, both glands work uncontrollably. The reasons are unclear, but genetic mutations probably play a role. Patients are then given lifelong drugs (aldosterone antagonists) that specifically neutralize the effect of the salt hormone. “In this way, the clinical picture can be well controlled,” says endocrinologist Petersenn.
Simpler laboratory tests should soon provide clarity more quickly. “Until now, diagnostics has far too often resembled a labyrinth,” says researcher Reincke. “We need urine tests that general practitioners can perform and that simultaneously target all hormonal blood pressure disorders.”
Another cause of high blood pressure can be too much adrenaline, the alarm hormone produced in the adrenal medulla. A usually benign adrenal tumor – the pheochromocytoma – then permanently fuels the release of adrenaline. As a result, blood pressure rises, the heart races, and you sweat. “High blood pressure with a high heart rate has two causes: an anxiety disorder – or pheochromocytoma,” says expert Petersenn.
Diagnostics are now less complicated than they used to be. Endocrinologists measure certain breakdown products of adrenaline in the blood. The therapy consists of the surgical, mostly minimally invasive removal of the tumor.
Patients are given special high blood pressure medication beforehand, which reverses the effects of adrenaline on the vessels. Otherwise, the tumors can massively increase blood pressure during anesthesia or surgery.
As common as Conn’s syndrome is, another hyperfunction is as rare: In Cushing’s syndrome, the adrenal glands flood the blood with cortisol. In the majority of cases, a benign tumor in the pituitary gland stimulates cortisol production in the adrenal gland. Years of cortisone use can also trigger Cushing’s.
Typical symptoms of cortisol excess are a round face, thin arms and legs, fat accumulation on the abdomen and neck, and red streaks on the skin. “Patients often describe that they can no longer climb the stairs because their muscles are fading,” reports expert Petersenn.
Cortisol also alters bone metabolism because it negates the effect of vitamin D – the risk of osteoporosis increases. “A classic case is that a 50-year-old patient comes with a vertebral fracture,” says the endocrinologist. In order to normalize the cortisol level, minimally invasive surgery is the method of choice for tumors. Alternatively, radiation or drug treatment can also be useful.
Studies have shown that people with adrenal disorders are more likely to have mental health problems. Virtually all Cushing’s patients suffer from memory disorders, 50 to 70 percent are depressed. “The chronic excess of the stress hormone cortisol increases the susceptibility to anxiety disorders and depression,” says expert Reincke.
Long-term observations show that the symptoms persist even after treatment of Cushing’s syndrome. The consumption of sleeping pills, tranquilizers and antidepressants is twice as high among those affected. “Apparently, the resistance of the psyche is reduced by high cortisol levels and remains so for life,” explains Reincke. An important goal is therefore to recognize the disease as early as possible so that psychotherapeutic treatment, as is common today, can take place promptly.
This article was written by Carolin Binder, Medical Editor
The original for this post “Tanned, listless and tired? An adrenal gland hypofunction could be the culprit” comes from FOCUS doctor search.
