Download Use of Human Parathyroid Hormone to Treat Hypoparathyroidism

Use of Human Parathyroid Hormone to Treat Hypoparathyroidism
By Jaffer Aldairi for the Alwasat Newspaper in Bahrain
(Please note the article was originally published in Arabic in Bahrain and was translated into
English.)
Parathyroid hormone was first synthesized in 1974 by Dr. John Potts at Massachusetts
General Hospital. But its use as a treatment for Hypoparathyroidism did not take place until January
1994 when it was used by Dr. Karen Winer at the National Institutes of Health in the United States.
Halla Ruth Halldórsdóttir, from Iceland, became the first child to use this medicine and became a
shining hope for more than 30 patients who participated in the protocol at NIH. It is human
synthetic parathyroid hormone in an injectible form, and all the patients responded to the treatment.
In the following interview conducted by the Alwasat newspaper and performed with the
cooperation of Hassan Fadhul and Dr. Winer, the doctor focuses the light on the new medicine in
honor of the precedence of its first use on one of her patients. Hassan Fadhul, a citizen of Bahrain,
has been diagnosed with Hypoparathyroidism and hopes the Bahraini Ministry of Health will
approved this new medicine.
What is your medical background?
I did my Residency at Mount Sinai Medical Center in New York. I started at the national
Institutes of health in 1990 as an Endocrine Fellow and have remained here to continue my research.
I worked with Dr. Gordon Cutler, Jr., M.D., who was my mentor during my fellowship and
afterwards. I am currently the program director for bone and mineral research for the National
Institutes of Child Health and Human Development.
Give us a short description of your new treatment for Hypoparathyroidism.
In 1993 I began a protocol to test human PTH 1-34 (hPTH 1-34) as a treatment for
Hypoparathyroidism. We were surprised that a single daily injection could maintain serum calcium in
the normal range for most of the day in patients with Hypoparathyroidism. In 1994 we started a
dose study to test the difference between once daily and twice daily PTH and found the twice daily
PTH provided more stable calcium levels throughout the 24-hour period.
How did you manage the use of the synthetic human parathyroid hormone to treat this
disease?
We had three protocols to treat patients with Hypoparathyroidism. The initial one was a
pilot study, the second a dose study, and the third a long-term treatment study. The results of all
three studies have been published.
Compare the differences between treatments with Vitamin D3 and the hPTH 1-34 injections.
We found that PTH 1-34 injections maintained serum calcium in the normal range in
patients with Hypoparathyroidism. In addition, it is a more physiologic approach and avoids the
elevated urine calcium levels that often occur with Vitamin D therapy. It therefore preserves kidney
function which is a great advantage. Several patients were not responding well to conventional
therapy (Rocaltrol [Calcitriol] and calcium supplements). PTH 1-34 injections enabled them to lead
normal lives.
Does the treatment of hPTH 1-34 have any disadvantages?
Twice daily subcutaneous injections may be regarded as a disadvantage for patients who
respond well to pills.
Is this treatment now currently under study? At what time will the old treatment be changed
to the new treatment using hPTH?
The FDA (Food and Drug Administration) has not approved this drug for use as a
treatment for Hypoparathyroidism. It has been approved for use in treating Osteoporosis.
If your experience to treat Hypoparathyroidism using hPTH 1-34 was successful, and
currently more than 30 patients have used the medication, why didn’t the FDA approve the
drug as a treatment for Hypoparathyroidism?
The FDA is concerned about the animal data which showed an increase incidence of bone
tumors with high doses of hPTH 1-34. They maintain that Calcitriol is good enough for most
patients.
We think that if the Ministry of Health in Bahrain read this article they may refuse the
treatment. Can you reassure the Ministry of health about the use of hPTH 1-34 as a
treatment for Hypoparathyroidism?
The conclusions of the animal study may not be relevant to humans with PTH deficiency.
They chose rats that are prone to tumor formation with normal parathyroid function. The animals
were given supraphysiologic doses of a hormone they did not need from the time of weaning.
Hassan’s doctor sent you a report about his case. What is your opinion?
As in other patients with Hypoparathyroidism, hPTH 1-34 should normalize his serum and
urine calcium levels.
Synthetic human Parathyroid Hormone was produced in 1974. Why haven’t doctors been
able to use this medicine to treat Hypoparathyroidism before your protocol?
hPTH 1-34 has a very short half-life and does not remain active in the blood for a long time.
Therefore researchers were concerned that multiple shots or a continuous infusion would be
necessary in order to maintain the serum calcium level in the normal range. It turns out that one or
two shots a day can maintain the serum calcium level in the normal range. This was a great surprise
to the medical community.
What is your advice to Hypoparathyroidism patients and doctors who still use the
conventional treatment?
To preserve kidney function, maintain serum calcium in the low-normal range and measure
urine calcium levels several times per year.