PART III: MEDICAL MANAGEMENT OF HYPERPARATHYROIDISM

PART III: MEDICAL MANAGEMENT OF HYPERPARATHYROIDISM

Synthesis done by
Kathryn P. Bongcawil, RN
Fatima Nur-Hayda V. Malali, RN
Jerrick Y. Medalla, RN


Regardless of age, surgery is recognized as the only definitive therapy for primary hyperparathyroidism, and patients with symptomatic hyperparathyroidism or documented complications should always be considered for parathyroidectomy.1

However, hyperparathyroidism is a common endocrine disorder that is frequently asymptomatic. In order to target surgery on those among the asymptomatic who are most at risk of complications of this disease, a set of guidelines is used, as originally recommended by a Consensus Development Conference on the Management of Asymptomatic Primary Hyperparathyroidism, held in 1990 at the National Institutes of Health2.

According to these guidelines, surgery is recommended as the primary
option in the following:
(i) those with a serum calcium more than 1 mg/dl above the upper limit of normal
(ii) those with any complication of primary hyperparathyroidism (such as overt bone disease or nephrolithiasis)
(iii) patients with an episode of acute primary hyperparathyroidism with life-threatening hypercalcemia,
(iv) patients with marked hypercalciuria (more than 400 mg daily excretion)
(v) those with a reduction in bone density.

Patients who are not considered for parathyroid surgery should remain well-hydrated and avoid immobilization. Particularly in older individuals, prompt medical attention for the possibility of worsening hypercalcemia is urged in the event of any serious illness accompanied by risk of dehydration.2

A moderate dietary calcium intake is recommended, although it remains unknown to what extent fluctuations in serum calcium in patients with primary hyperparathyroidism are a function of dietary calcium intake.3 Medical follow-up usually includes visits twice yearly with determinations of serum calcium and urinary calcium excretion. Yearly bone densitometry is also recommended.2

Effective therapeutic agents for the long-term medical management of primary hyperparathyroidism are not available yet. A more targeted approach to the medical therapy of primary hyperparathyroidism would be to interfere specifically with the production of PTH.4

Bone protection is of prime importance in over-active PTH production, as it has long-term detrimental effects on bone density. Apart from definitive surgery, medical therapy to protect bone is worth considering, and benefit may be achieved with bisphosphonates and hormone replacement therapy in post-menopausal women. This is where pharmacological intervention comes into play. As indicated above, long-term follow-up is essential, as recurrence can occur up to 30 years later.5

Booner, Vanderschueren, Pelemans, and Boullion (2004) suggest that patients with Primary Hyperparathyroidism should be well-hydrated especially the elderly since they are prone to dehydration. They should also be kept mobile. Avoidance of Thiazide Diuretics need to be practiced since it increased hypercalcemia. Moderation inCalcium in the diet need to be observed. Yearly Bone Densitometry and biannual medical check-up is essential for these patients. According to them, Biphosphonates Alendronate and Risedronate are recommended as medical management to elderly suffering from Hyperparathyroidism. But during the first year of treatment, the latter is known to be more tolerated by the elderly, with less boneturnover, and it is said to cause improvement in Bone Density at the lumbar area. Serum Calcium was also noted to be decreasing with these medications but not to the normal ranges 6.

The author of another journal also tackled about medications to address Hyperparathyroidism. Cinacalcet was cited to treat Primary and Secondary Hyperparathyroidism in adults. Calcitriol is given through parenteral route for Secondary Hyperparathyroidism in patients undergoing Hemodialysis and orally to Peritoneal Dialysis patients but it results to increased circulating Calcium in the blood, thus, Vitamin D analog (Paricalcitol) should be ready on-hand as antidote. This Vitamin D treats Secondary Hyperparathyroidism without causing Calcium and Phosphorus levels to increase. The Autor seconded that of Booner et. al.’s study that Biphosphonated be used and mobilization should be encouraged especially in children to reduced Calcium levels 7.

Norman (2008) shares that there had been studies that Sensipar (Cinacalcet) decreases Calcium levels but also causes a Hyperparathyroid patient’s osteophorosis worsen or may even lead to bone loss. The authors think that other side effects of this drug outweighs the benefit 8.

Japanese nephrologists recommended that serum calcium and phosphate concentrations should be normalized and then the patient be treated by administration of ‘physiological’ doses of active vitamin D sterols. Then go on to calcitriol pulse therapy either by intravenous or oral routes. When this approach is used, suppression of PTH secretion can be achieved early on and will usually persist in the long run. In order to prevent the progression from diffuse to nodular hyperplasia, that rigorous control of serum phosphate concentration is indispensable, based on animal experiments indicating that high phosphate concentrations stimulate the parathyroids It is of interest that according to Almaden et al.the stimulatory effect of phosphate is more pronounced in parathyroid tissue exhibiting diffuse rather than nodular hyperplasia. A phosphate load also contributes to decreased calcium sensing receptor expression. (M. Fukagawa, J. Kazama and T. Shigematsu ROD-21 Clinical Research Group, Japan).

This study is supported by Khan AA. a review( Endocrine Practice 1997;3:22-6.) they conclude that Calcimimetic agents mimic the effect of calcium at the calcium receptor. One such agent is the phenylalkylamine compound, which has been shown in animal studies to be effective in decreasing cytoplasmic calcium levels, PTH secretion and serum calcium levels. It has shown to reduce PTH secretion and ionized calcium levels in 20 postmenopausal women with asymptomatic primary hyperparathyroidism.

On the other hand surgical management by Melton LJ III Journal of Bone Mineral Research 2002 suggest that the best choice for managing patients with sporadic asymptomatic primary hyperparathyroidism in the absence of a randomized clinical trial comparing all the therapeutic strategies minimally invasive surgical strategies to be more effective than the traditional bilateral neck exploration. While it is contradicted by another study In patients with primary hyperparathyroidism, surgical removal of all pathologic parathyroid tissue is the only definitive therapy that leads to normalization of PTH and calcium levels and to a durable cure. Successful parathyroidectomy also reverses the accelerated bone loss, diminishes future risk for renal calculi and results in disappearance of the wide spectrum of non specific symptoms associated with hyperparathyroidism. Preoperative localization of parathyroid glands is no substitute for surgical experience 9.



REFERENCES:

1 Birkenhager JC & Bouillon R. Asymptomatic primary hyperparathyroidism.
Postgraduate Medical Journal 1996 72 323–326. Retrieved on February 16, 2010 at www.eje-online.org

2 Consensus Development Conference Panel, Diagnosis and management of asymptomatic primary hyperparathyroidism: Consensus Development Conference Statement. Annals of Internal Medicine 1991 114 593–597

3 Bilezikian JP. Management of hypercalcemia. Journal of Clinical Endocrinology and Metabolism 1993 77 1445–1449. Retrieved on February 16, 2010 at
http://jcem.endojournals.org/

4 Deftos LJ, Partemore JG & Stabile BE. Management of Primary Hyperparathyroidism. Annual Review of Medicine 1993 44 19–26.

5 Diamond T, Ng A, Levy S et al. Oestrogen therapy may be an alternative to parathyroid surgery for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism: a preliminary report. Osteoporos Int 1996; 4: 329-33.

6 Booner, S., Vanderschueren, D., Pelemans, W., and Buillon, R. (2008). Primary
Hyperpathyroidism’s Diagnosis and Management in Older Individuals.
European Journal of Endocrinology, 151 297-304. Retrieved form
Eje-online.org

7 Klein, G. (2008). Hyperparathyroidism: Treatment And Medication. Retrieved February 17,
2010 from http://emedicine.medscape.com/article/921453-treatment

8 Norman, J. (2008). Minimally Invasive Surgery of the Parathyroid: Treatment: Medication.
Retrieved on February 17, 2010 from http://emedicine.medscape.com/article/1298768-treatment

9 Melton LJ III. The epidemiology of primary hyperparathyroidism in North America. Journal of Bone Mineral Research 2002 17 (Suppl 2) N12–N17.

10 Adami S, Marcocci C & Gatti D. Epidemiology of primary hyperparathyroidism in Europe. Journal of Bone Mineral Research 2002 17 (Suppl 2) N18–N23.

11 Bilezikian JP, Potts JT Jr, Fuleihan G, Kleerekoper M, Neer R, Peacock M, Rastad J, Silverberg SJ, Udelsman R &Wells SA. Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. Journal of Clininical Endocrinology & Metabolism 2002 87 5353–5361.

12 Silverberg SJ & Bilezikian JP. Evaluation and management of primary hyperparathyroidism. Journal of Clinical Endocrinology & Metabolism 1996 81 2036–2040.

13 Udelsman R. Surgery in primary hyperparathyroidism: the patient without previous neck surgery. Journal of Bone Mineral Research 2002 17 (Suppl 2) N126–N132.

14 Denham DW & Norman J. Cost-effectiveness of preoperative sestamibi scan for primary hyperparathyroidism is dependent solely upon the surgeon’s choice of operative procedure. Journal of the American College of Surgeons 1998 186 293–305