Hyperparathyroidism and Diabetes Mellitus
The co-existence of hyperparathyroidism and diabetes mellitus merits special mention. The prevalence of hyperparathyroidism amongst diabetic patients is higher than that in general population and the prevalence of diabetes amongst patients with hyperparathyroidism is higher than that in general population. Hyperparathyroidism, with or without diabetes, is almost three times more common in females and nearly seven times more common in post-menopausal women.
In Canada, the prevalence of diabetes mellitus in patients with primary hyperparathyroidism is approximately 8%, and that of primary hyperparathyroidism in diabetic patients around 1%. Both values are about three-folds higher than the respective prevalence of each condition in the general population. Most patients harbouring both disorders are over 40 years of age and 80% are female; 22% have type 1 and 78% have type 2 diabetes. Primary hyperparathyroidism manifests first in nearly 20% of patients, and diabetes mellitus manifests first in 40%; both disorders present together, or within 1 year of each other, in the remaining 40%. In the United States, in a population-based study from Olmsted County, Minnesota, the prevalence of primary hyperparathyroidism was reported to be 21 cases per 1,00,000 person years. The authors suggested a trend towards a decrease in the prevalence. The average age at diagnosis was 54 years, and female patients were three times more than the number of males.
Approximately 40% of patients with primary hyperparathyroidism have impaired glucose tolerance. Insulin resistance present in patients with hyperparathyroidism probably arises from a raised intracellular free calcium concentration, which reduces insulin-stimulated glucose transport. With the progression of insulin resistance, impaired glucose tolerance, and finally diabetes mellitus may result. Parathyroidectomy has been followed by regression of diabetes and impaired glucose tolerance in some but not all patients. Hyperparathyroid patients should therefore be screened for impaired glucose tolerance and diabetes mellitus annually, and pre-operatively.
Although some reports suggest a benefit of parathyroidectomy on improvement of glycaemic control, others do not. Some authors have even suggested parathyroidectomy for the treatment of diabetes mellitus. In an observational study of 36 insulin-requiring diabetic patients undergoing curative parathyroidectomy from 1970 to 1984 at Mayo Clinic, Rochester, USA, no correlation was found between parathyroidectomy and reduction of dose of insulin.
In the year 2002, the National Institutes of Health of USA developed a list of criteria for surgery in asymptomatic individuals with primary hyperparathyroidism (any one of the following):
- Blood calcium level > 1.0 mg/dl above normal
- 24-hour urinary calcium excretion > 400 mg
- Renal function reduced by 30% or, more
- Bone mineral density reduced by 2.5 standard deviation below young healthy controls
- Age less than 50 years
- A single Parathyroid adenoma in about 85% of cases; in approximately 15% of cases, multiple glands may be affected. Familial cases can be a part of Multiple Endocrine Neoplasia type 1 (MEN1)
- Parathyroid hyperplasia (~2.5%)
- Carcinoma of parathyroid (<1%)
Diagnosis of Hyperparathyroidism
Symptoms: Many individuals with hyperparathyroidism may remain asymptomatic. The symptoms of hyperparathyroidism are related to hypercalcaemia and include
- General weakness; lethargy; muscle weakness
- Polyuria and polydipsia
- Anorexia, vomiting, abdominal pain and constipation
- Depression, psychosis and memory loss
- Bone and joint pain
It is interesting to note that almost all the above symptoms may be present in an uncontrolled diabetic patient.
Laboratory Diagnosis of Hyperparathyroidism
The cardinal feature of diagnosis of primary hyperparathyroidism is the demonstration of an elevated parathyroid hormone (PTH) value in the blood together with hypercalcaemia. Differential diagnosis of hypercalcaemia with an elevated PTH value are:
- Patients receiving Lithium therapy
- Familial benign hypercalcuric hypercalcaemia (FHH)
A group of patients may have serum calcium levels in the normal range with high PTH level in blood – the so called normocalcaemic hyperparathyroidism. In such cases, other secondary causes of high PTH level (Low calcium intake, chronic diarrhoea, renal insufficiency, Vitamin D deficiency) should be ruled out.
Laboratory Work Up
- Total serum calcium and albumin level or, ionized calcium will be high. When confirmed by a repeat value, serum PTH should be measured.
- Serum PTH level – assay of whole or “intact” PTH level. The 1st generation assay method of fragmented PTH molecule assay has become obsolete.
- Imaging studies – necessary when surgical removal of parathyroid gland is contemplated. Radiolabelled sestamibi accumulates in thyroid and parathyroid gland but washes out under an hour. It persists in abnormal parathyroid tissue. The sensitivity of this radionuclide scan in detecting a solitary adenoma varies between 60 – 90%. But in cases of multiple tumours, the sensitivity drops to 50%. In such situations, a SPECT scan, or dynamic contrast CT scan (4D-CT), or MRI scan can increase the sensitivity.
^ Taylor, WH, Khaleeli, AA. Coincident diabetes mellitus and primary hyperparathyroidism. Diabetes Metab. Res. Rev. 2001; 17: 175–180.
^ Wermers RA, Khosla S, Atkinson EJ, Achenbach SJ, Oberg AL, Grant CS. Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993 – 2001: an update one the changing epidemiology of the disease. J Bone Minr Res. Jan 2006; 21(1):171-177.
^ Bannon MP, van Heerden JA, Palumbo PJ and Ilstrup DM (1988), The relationship between primary hyperparathyroidism and diabetes mellitus. Ann. Surg. April 1998; 207(4): 430 – 433.