Other Metabolic Diseases



Advises Mr. George Trovas, Endocrinologist, Supervisor Collaborator of Musculoskeletal Diseases Research Laboratory

Primary hyperparathyroidism is the third most common endocrine disorder. It most commonly affects women, especially in the early postmenopausal years, with a ratio of women/men of about four to one.

Primary hyperparathyroidism is usually due to solitary parathyroid adenoma (approximately 80%), with multiple adenomatous disease being found in 15-20% of patients, while parathyroid cancer is rare (<1%

of all cases of primary hyperparathyroidism). In most patients with primary hyperparathyroidism the disease is sporadic, with no family history or history of other endocrine diseases.

Asymptomatic primary hyperparathyroidism is the most common form of the disease in most countries, and less commonly the disease may be presented with symptoms. Systems and organs that may be affected by primary hyperparathyroidism include:

  • the musculoskeletal system, with proximal muscle weakness, neuromuscular manifestations, gait disorder, muscle atrophy
  • bones, with a characteristic clinical manifestation of osteitis fibrosa cystica, which is characterized by a picture of salt and pepper on X-rays of the skull, a picture of bone resorption, the development of bone cysts and brown tumors. These bone lesions can lead to skeletal deformities, fractures, and severe bone pain.
  • kidneys, with the development of nephrolithiasis, kidney calcification and decreased renal function
  • the gastrointestinal tract, at risk of developing peptic ulcer and acute pancreatitis
  • the cardiovascular system, with the development of hypertension, left ventricular hypertrophy and atherosclerosis, and
  • cognitive disorders such as anxiety disorder and reduced ability to concentrate.

Finally, although patients with primary hyperparathyroidism usually may not have clinical manifestations from the aforementioned target organs, they may report more vague and non-specific symptoms, making it difficult to diagnose the disease. For example, many patients report fatigue and difficulty concentrating, so we need to be vigilant and well informed.

Skeletal involvement in primary hyperparathyroidism, even among patients with asymptomatic disease, can be detected by imaging techniques such as bone mineral density and X-rays.

In these cases, the first clinical manifestation is usually a fracture. It should be noted that patients with primary hyperparathyroidism may present with low bone density globally, while areas of the forearm and less of the lumbar spine appear to be typically affected.

In fact, a characteristic feature of lumbar spine involvement is the increased risk of vertebral fractures in patients with primary hyperparathyroidism. With the above in mind, we understand the importance of examining the condition of our bones, with the help of a specialist, even if the primary hyperparathyroidism occurs without or with atypical symptoms.

The “hungry bone” syndrome

Finally, a special feature of skeletal involvement in the case of severe primary hyperparathyroidism is hungry bone syndrome. It is characterized by prolonged low levels of calcium and phosphorus in the blood, after surgical removal of the parathyroid glands, as a result of the rapid transport of calcium salts to the bone. In many cases, intravenous and prolonged administration of calcium and vitamin D may be required to restore normal calcium levels.

Patients with primary hyperparathyroidism typically have elevated levels of calcium and parathyroid hormone at levels that are above normal in mild cases to very high levels in cases of severe disease. Low phosphorus levels are also common. Finally, in these patients, vitamin D needs to be measured, as well as assessment of renal function and measurement of 24-hour urinary calcium.

The only definitive treatment for primary hyperparathyroidism is surgical removal of the overactive parathyroid gland. Bone disease is an indication for parathyroidectomy, even in the case of asymptomatic hyperparathyroidism.

For this reason, as mentioned before, it is very important to assess the condition of our bones, with the help of a specialist, even if the primary hyperparathyroidism occurs with or without atypical symptoms. Bone density improves in the first years after surgery, increasing by up to 12% in both the lumbar region of the spine and the hip area. In case the surgical treatment is not indicated, due to co-existing serious diseases of the patient or due to the patient’s desire not to undergo surgery, there is an alternative drug treatment, which should be known that does not ensure the definitive treatment of primary hyperparathyroidism.

In conclusion

Adequate dietary calcium intake and vitamin D intake are therefore recommended to maintain 25 (OH) levels of vitamin D in the blood between 20-30ng/mL, with close monitoring of plasma and urine calcium levels. Finally, specialized drugs that aim to keep our skeleton in as good condition as possible and to correct calcium levels can be administered, always with the guidance of a specialist, after our valid information on how they work and the treatment plan that exists by the specialist for each patient individually.



Advises Mr. Konstantinos Dion. Stathopoulos, Orthopedic Surgeon

Member of the Hellenic Society of Orthopedic Surgery and Traumatology, of the Hellenic Society for the Study of Bone Metabolism, and of the International Society of Musculoskeletal & Neuronal Interactions (ISMNI), associate of the Medical School of the University of Athens “Metabolic Diseases of Bones” and the Research Laboratory of Research and Education “Th. Garofalidis”.

What is algodystrophy?

The term algodystrophy has been used many times in the past in the Greek and international literature to describe painful syndromes of the upper or lower limbs, which sometimes invade suddenly and without a history of injury and other times after injury or fracture or some kind of minor orthopedic surgery. The term is found in 17th and 18th century’s medical texts, where it was originally associated with peripheral nerve injury, and in the early 20th century Sudeck used it to describe a painful syndrome as a complication after a limb fracture without nerve injury.

The term transient osteoporosis, on the other hand, was used in the English literature in 1959 by Curtis and Kincaid, who described a small group of 3 women who developed hip pain and osteopenia in the last trimester of pregnancy, whose symptoms and radiological changes disappeared automatically after a few months. It is now clear that algodystrophy and transient osteoporosis are distinct syndromes, which as a common feature may have at some point in time the radiographic picture of osteopenia of the affected bones, however they present significant differences and should not be confused with each other.



Advises Mr. George Trovas, Endocrinologist, Laboratory of Research of Musculoskeletal Diseases “Th. Garofalidis”

What is beta thalassemia major?

Hemoglobinopathies are the most commonly inherited genetic disorders worldwide. Beta-thalassemia is caused by mutations in the hemoglobin β-chain gene. The clinical picture of β-thalassemia varies from asymptomatic, in the case of stretch marks (β-thalassemia minor) to severe clinical picture with anemia and skeletal abnormalities in the case of β-thalassemia major.

How is it diagnosed?

The diagnosis of β-thalassemia major is usually made in children under 2 years of age who present with severe anemia, jaundice, and enlarged liver and spleen. The diagnosis is confirmed by the detection of low hemoglobin A levels on hemoglobin electrophoresis.

Before blood transfusions became possible, β-thalassemia major  was fatal in the first decade of life. However, after the intensification and optimization of transfusion programs, there was a significant improvement in the prognosis of these patients, with a significant prolongation of their survival and remission of the clinical manifestations of the disease.

One of the main problems that characterizes major β-thalassemia is severe anemia. In its attempt to deal with this condition, the body overgrows the bone marrow in order to produce red blood cells. This can lead to significant bone marrow expansion up to 15-30 times.

In addition, the liver and spleen swell in an attempt to take part in redness as the bone marrow fails to raise hemoglobin levels satisfactorily. At the same time, the important clinical manifestations of the disease include skeletal manifestations. As already mentioned, before the era of systemic transfusions, the body’s attempt to treat severe anemia led to hyperplasia of the bone marrow, resulting in skeletal manifestations of the disease.

In these patients, cranial deformities, spinal abnormalities, scoliosis and severe osteoporosis were common manifestations, with a fracture rate of 30% -50%. In fact, this significant expansion of the bone marrow, led to thinning of the bone cortex which was particularly evident in the skull, long bones, vertebral bodies, ribs and pelvis.

In addition, extra-medullary hematopoietic tissue sometimes developed, below the periosteum or in the form of large intrathoracic masses/pseudo-tumors, consisting of overdeveloped hematopoietic tissue.

However, the systematic use of transfusions that suppress bone marrow hyperplasia has significantly improved survival and skeletal manifestations in patients with major β-thalassemia. However, there are still findings of low bone density, bone algae and increased fracture risk in these patients, even today.

Infection of bone tissue in major β-thalassemia is the result of many parameters, including:

  • underlying genetic mutations
  • the clinical phenotype
  • the age
  • the sex of the patient
  • the type of treatment and the frequency of transfusions
  • any side effects of iron removal treatment and
  • any endocrine complications associated with vitamin D deficiency, zinc deficiency, iron overload and
  • reduced physical activity.

Bone disease in β-thalassemia major is a disease that occurs from  childhood. Childhood is important for gaining top bone mass. However, the exact mechanisms of reduced bone mass in the case of thalassemia patients have not been fully elucidated. To some extent it seems to be responsible for the increased bone resorption, as well as the hyperplasia of the bone marrow, with the concomitant secretion of cytokines that stimulate bone resorption. In addition, the concomitant hypogonadism that may coexist in these patients promotes bone resorption.

As previously reported, prior to intensification of transfusions, patients with β-thalassemia major had severe anemia and severe skeletal deformity due to bone marrow expansion as a result of ineffective erythropoiesis. This hyperplasia of the bone marrow led to thinning of the bone cortex, absorption of the cancellous bone, and extensive bone loss.

The treatment of the disease

However, in the modern era of treating thalassaemic patients with transfusions and iron deprivation regimens, the above clinical picture is now rare. However, even today, it seems that thalassaemic patients are still prone to bone loss as transfusions do not appear to be sufficient to completely suppress bone marrow stimulation.

On the other hand, an important problem of continuous transfusions is the overload of the body with iron. Iron accumulates in the hepatocytes, leading to fibrosis and cirrhosis of the liver. Also, the accumulation of iron in the liver has been associated with an increased risk of endocrine diseases, bone disease and heart disease.

For this reason, drugs are used that bind and remove iron from the body of polytransfused patients, which should also be administered with caution due to the negative effects they may have on the skeleton. These drugs can lead to the development of nephrolithiasis and impaired renal function, as well as loss of bone tissue.

As for endocrine diseases as a complication of iron overload, the most common is hypogonadism. The negative effects of skeletal hypogonadism are known in both women and men, leading to an increased risk of osteopenia, osteoporosis and fractures.

Growth hormone deficiency is also another endocrinopathy that can occur due to the body overloading with iron. The involvement of growth hormone in the acquisition of peak bone mass during skeletal development as well as its involvement in the maintenance of bone mass in adulthood is well known. Its deficiency results in an increased risk of osteoporosis and fractures.

Finally, other endocrine diseases such as hypothyroidism, hypoparathyroidism and insulin-dependent diabetes mellitus may occur less frequently.

In addition, another problem of thalassemia patients is their poor diet and reduced physical activity, especially during the period of skeletal development.

The important role that both diet and physical activity play in the normal development of the skeleton is well known. For this reason, thalassemia patients should be provided with adequate levels of important nutrients such as vitamins (A, C, D, E, K, folic acid, thiamine, B12, calcium, magnesium, etc.), as well as regular physical activity.

In conclusion:

In conclusion, it should be noted that the main concern of patients with major β-thalassemia major is the optimization of bone health, especially during skeletal development. Control of anemia with transfusions, removal of excess iron from the body with iron deficiency treatments, proper nutrition, nutritional supplements such as calcium and vitamin D, where needed, and regular physical exercise are the key measures to protect skeletal health. Finally, anti-osteoporotic drugs such as bisphosphonates etc. can be used to treat severe bone loss.

In the near future, new treatment options revealed by new studies may help reduce the effect of β-thalassemia major on the skeleton and ensure its protection from the negative effects of the disease.



Advises Mr. George Trovas, Endocrinologist, Laboratory of Research of Musculoskeletal Diseases “Th. Garofalidis”

Anorexia nervosa is an eating disorder characterized by:

  • great weight loss with a value of Body Mass Index <17.5 FT (18.5-25)
  • amenorrhea (at least 3 discharges)
  • distorted body image with the feeling that there is excess fat even when the body is bony
  • Depressed mood, insomnia, irritability, decreased sexual desire, dry skin.

Anorexia nervosa is a disease that affects the function of many organs and tissues of the human body including bones. Although it affects both sexes, it is 10 times more common in women compared to men and usually the onset of the disease begins at the age of 16-17 years.

The reasons that this disease has a detrimental effect on the skeleton are:

Hormones: In girls, the lack of estrogen that characterizes the disease and causes menstrual disorders has a negative effect on bone growth, especially during adolescence, resulting in low bone density and endurance. Similarly, low testosterone levels negatively affect boys’ bone health. There are also low levels of insulin-like growth factor, a hormone that is important for growth and its reduction has a negative effect on skeletal growth as well as hypercortisolemia, another hormone that has a negative effect on bone metabolism.

Low body weight: Low weight has an immediate detrimental effect on bones and is an important factor in osteoporosis and increased risk of fracture even for people without anorexia nervosa.

Poor diet: Due to limited food prevention, people with anorexia nervosa do not receive the proper nutrients necessary for the skeleton (Calcium, Vitamin D, protein, and other important minerals and trace elements).


Early diagnosis is important because the loss of bone density can occur very early in the course of the disease.

  • The necessary examinations include the measurement of bone density in the context of the investigation of the disease with special attention to its interpretation when it comes to developing skeleton.
  • Restoring body weight and hormones to normal levels is the cornerstone of treating anorexia nervosa.
  • A balanced diet rich in calcium, vitamin D, protein and other trace elements is recommended.
  • Adopting a healthy lifestyle by avoiding smoking and alcohol will help a lot.
  • Although exercise is necessary for the skeleton it needs to be done prudently, in order to avoid physical exertion that can lead to opposite results.
  • Currently there are no approved drugs to treat osteoporosis, especially in anorexia nervosa but there are ongoing studies.
  • Hormone administration is generally not recommended, although studies with transdermal estrogen during adolescence show that they return their levels to normal.