Annals of the Royal College of Surgeons of England
(I979)
vol 6i
ASPECTS OF DIAGNOSIS*
The diagnosis of primary hyperparathyroidism James S Hilary Wade MC TD FRCS Consultant Surgeon, University Hospital of Wales, Cardiff
Summary
the parathyroid glands becoming autonomous; in fact a parathyroid tumour has developed in the hyperplastic parathyroid tissue or the hyperplastic glands themselves have become autonomous. This tissue behaves like a primary tumotur or primary hyperplasia and the excess PTH results in hypercalcaemia. This syndrome is known as tertiary hyperparathyroidism. In this paper I shall discuss only the diagnosis of primary hyperparathyroidism. There are clinical features which arouse suspicion, Introduction but diagnosis depends upon laboratory Hyperparathyroidism is a disease in which the tests atofirm detect the hypercalcaemia and the inparathyroid tissue is overactive and produces creased secretion of PTH. an excess of parathyroid hormone (PTH). There are three forms of hyperparathyroid- Clinical features ism-primary, secondary, and tertiary. Pri- These may be divided into four groups. mary hyperparathyroidism is most commonly I) SYMPTOMS DUE TO HYPERCALCAEMIA AND due to a parathyroid adenoma, and in 3 o of HYPERCALCIURIA cases more than one adenoma is present. Idio- These include thirst, polyuria, psychiatric dispathic or unexplained hyperplasia of all four orders such as depression and anxiety, fatigue, parathyroids is an occasional cause and a very and Vomiting leads to dehydration occasionaal one is a parathyroid carcinoma. In and vomiting. this increases the hypercalcaemia; this primary hyperparathyroidism the excess PTH may lead to a parathyroid crisis. produced by the tumour or by hyperplasia re2) VISCERAL CALCIFICATION sults in hypercalcaemia (Fig. i.) Some degree of renal calcification is common. Secondary hyperparathyroidism is due to a It is irreversible and, if severe, it results in compensatory hyperplasia of all four glands. If and renal failure. This progresshypertension the body has a calcium deficiency because of ive renal damage provides a powerful argurenal damage or because the intake of calcium ment in favour of early operation once the is reduced on account of intestinal malof diagnosis hyperparathyroidism has been calcium in the serum the fall conabsorption established. As a result of renal calcification centration stimulates the parathyroid glands renal colic and renal stones are common. and they become hyperplastic. This secondary PRIMARY hyperplasia results in a rise in secretion of PTH ) * Adenoma which, by resorption of bone, brings the serum * Carcinoma ) P T H t and Se Cat * Hyperplasia calcium level back to normal. Thus in secondary hyperparathyroidism there is an excess SECONDARY production of PTH, but it does not result in * Compensatory Hyperplasia P T H t and Se Ca Certain clinical features arouse suspicion of primary hyperparathyroidism, but a firm diagnosis depends upon laboratory tests. Hypercalcaemia associated with a raised or detectable level of parathyroid hormone (PTH) in the serum is diagnostic. Facilities for obtaining PTH estimations are available everywhere in the United Kingdom through the Supraregional Assay Service.
hypercalcaemia. TERTIARY Sometimes the prolonged stimulation of the *Autonomous Adenoma in Hyperplastic Gland P T H t and Se Cat *Autonomous Hyperplastic Glands parathyroid tissue that occurs in secondary hyperparathyroidism results in one or more of FIG. I Types of hyperparathyroidism. The Editor would welcome any observations on this paper from readers *Fellows and Memb'rs interested in submitting papers for consideration with a view t publication in this series should first write to the Editor.
The diagnosis of primary hyperparathyroidism
Calcification sometimes occurs in the cornea as a visible band. Severe earache from calcification of the eardrum may be a presenting symptom and calcification may also occur in the cartilage of the ear or in joints. 3) BONE RESORPTION The very severe bony changes of osteitis fibrosa cystica-described by von Recklinghausen-are rarely seen today. In this condition prolonged decalcification and cyst formation resulted in gross skeletal deformity. We do sometimes see a giant-cell tumour or quite large cysts, and occasionally a pathological fracture occurs at the site of a cyst. Nowadays, however, bone resorption usually produces a painful generalised osteoporosis and this is a common presenting symptom. These patients frequently have spinal deformity (Fig. 2). One of the earliest X-ray findings is subperiostal erosion in the phalanges of the fingers, particularly the middle phalanx of the index finger on the radial side. Decalcification of the skull bones, producing a pepper-pot appearance, is another early finding.
363
cardiac arrest may occur. This is a surgical emergency and immediate operation is essential after rehydration of the patient to lower the serum calcium level. When hyperparathyroidism was first recognised patients presented either with renal stones or with gross bony changes. However, the symptoms of hyperparathyroidism are so diverse that none are typical of the disease and the patient may be referred to any specialist clinic that you can mention. In fact, today in the United Kingdom the commonest presentation is the patient with no definite symptoms who is found by chance to have a raised serum calcium level. Laboratory tests A firm diagnosis cannot be made on clinical features alone. Diagnosis is made either because clinical suspicion leads to a serum calcium estimation or because of the chance finding of a raised serum calcium level. In the category of clinical suspicion are patients with renal stones or renal colic, those with osteoporosis, and, to a lesser extent, patients with a peptic ulcer or with acute pancreatitis. All such patients should be screened for hyper4) MISCELLANEOUS GROUP Peptic ulceration sometimes occurs; it is prob- parathyroidism. ably due to stimulation of gastrin-secreting cells by the hypercalcaemia. Acute pancreatitis is another unusual presentation. Only rarely is a parathyroid tumour large enough to be palpated clinically. Rare too is the incidence of the multiple endocrine neoplasia (MEN) syndrome which is often associated with a parathyroid tumour or parathyroid hyperplasia. A rare but very interesting presentation is neonatal tetany in a baby born to a mother with unsuspected hyperparathyroidism. Because the mother has hypercalcaemia and the calcium crosses the placenta the serum calcium concentration of the developing fetus is also raised so that the fetal parathyroid glands are suppressed. Soon after birth the baby becomes hypocalcaemic and it is some days before its suppressed parathyroid glands recover. Parathyroid crisis is due to a marked hypercalcaemia-usually with a serum calcium level approaching 4 mmol/l (I6 mg/Ioo ml). Nausea and vomiting are the principal symptoms and the resulting dehydration increases the FIG. 2 Gross spinal deformity in a 70-year-old serum calcium level to such an extent that woman with a large parathyroid adenoma.
364
James S Hilary Wade DIAGNOSIS CERTAIN
activity-as occurs, for example, in thyrotoxicosis. It is important to appreciate that if * Hypercalcaemia a patient has hypercalcemia due to any cause other than hyperparathyroidism PTH cannot + Raised P T H i. e. > 1. 0 ng/ml. be detected in the serum. The reason for this is the feedback mechanism between paraOR thyroid activity and the serum calcium level: * Hypercalcaemia parathyroid secretion is suppressed by a raised + Normal (but detectable) P T H serum calcium level unless one or more of the i.e.
(I979)
vol 6i
ASPECTS OF DIAGNOSIS*
The diagnosis of primary hyperparathyroidism James S Hilary Wade MC TD FRCS Consultant Surgeon, University Hospital of Wales, Cardiff
Summary
the parathyroid glands becoming autonomous; in fact a parathyroid tumour has developed in the hyperplastic parathyroid tissue or the hyperplastic glands themselves have become autonomous. This tissue behaves like a primary tumotur or primary hyperplasia and the excess PTH results in hypercalcaemia. This syndrome is known as tertiary hyperparathyroidism. In this paper I shall discuss only the diagnosis of primary hyperparathyroidism. There are clinical features which arouse suspicion, Introduction but diagnosis depends upon laboratory Hyperparathyroidism is a disease in which the tests atofirm detect the hypercalcaemia and the inparathyroid tissue is overactive and produces creased secretion of PTH. an excess of parathyroid hormone (PTH). There are three forms of hyperparathyroid- Clinical features ism-primary, secondary, and tertiary. Pri- These may be divided into four groups. mary hyperparathyroidism is most commonly I) SYMPTOMS DUE TO HYPERCALCAEMIA AND due to a parathyroid adenoma, and in 3 o of HYPERCALCIURIA cases more than one adenoma is present. Idio- These include thirst, polyuria, psychiatric dispathic or unexplained hyperplasia of all four orders such as depression and anxiety, fatigue, parathyroids is an occasional cause and a very and Vomiting leads to dehydration occasionaal one is a parathyroid carcinoma. In and vomiting. this increases the hypercalcaemia; this primary hyperparathyroidism the excess PTH may lead to a parathyroid crisis. produced by the tumour or by hyperplasia re2) VISCERAL CALCIFICATION sults in hypercalcaemia (Fig. i.) Some degree of renal calcification is common. Secondary hyperparathyroidism is due to a It is irreversible and, if severe, it results in compensatory hyperplasia of all four glands. If and renal failure. This progresshypertension the body has a calcium deficiency because of ive renal damage provides a powerful argurenal damage or because the intake of calcium ment in favour of early operation once the is reduced on account of intestinal malof diagnosis hyperparathyroidism has been calcium in the serum the fall conabsorption established. As a result of renal calcification centration stimulates the parathyroid glands renal colic and renal stones are common. and they become hyperplastic. This secondary PRIMARY hyperplasia results in a rise in secretion of PTH ) * Adenoma which, by resorption of bone, brings the serum * Carcinoma ) P T H t and Se Cat * Hyperplasia calcium level back to normal. Thus in secondary hyperparathyroidism there is an excess SECONDARY production of PTH, but it does not result in * Compensatory Hyperplasia P T H t and Se Ca Certain clinical features arouse suspicion of primary hyperparathyroidism, but a firm diagnosis depends upon laboratory tests. Hypercalcaemia associated with a raised or detectable level of parathyroid hormone (PTH) in the serum is diagnostic. Facilities for obtaining PTH estimations are available everywhere in the United Kingdom through the Supraregional Assay Service.
hypercalcaemia. TERTIARY Sometimes the prolonged stimulation of the *Autonomous Adenoma in Hyperplastic Gland P T H t and Se Cat *Autonomous Hyperplastic Glands parathyroid tissue that occurs in secondary hyperparathyroidism results in one or more of FIG. I Types of hyperparathyroidism. The Editor would welcome any observations on this paper from readers *Fellows and Memb'rs interested in submitting papers for consideration with a view t publication in this series should first write to the Editor.
The diagnosis of primary hyperparathyroidism
Calcification sometimes occurs in the cornea as a visible band. Severe earache from calcification of the eardrum may be a presenting symptom and calcification may also occur in the cartilage of the ear or in joints. 3) BONE RESORPTION The very severe bony changes of osteitis fibrosa cystica-described by von Recklinghausen-are rarely seen today. In this condition prolonged decalcification and cyst formation resulted in gross skeletal deformity. We do sometimes see a giant-cell tumour or quite large cysts, and occasionally a pathological fracture occurs at the site of a cyst. Nowadays, however, bone resorption usually produces a painful generalised osteoporosis and this is a common presenting symptom. These patients frequently have spinal deformity (Fig. 2). One of the earliest X-ray findings is subperiostal erosion in the phalanges of the fingers, particularly the middle phalanx of the index finger on the radial side. Decalcification of the skull bones, producing a pepper-pot appearance, is another early finding.
363
cardiac arrest may occur. This is a surgical emergency and immediate operation is essential after rehydration of the patient to lower the serum calcium level. When hyperparathyroidism was first recognised patients presented either with renal stones or with gross bony changes. However, the symptoms of hyperparathyroidism are so diverse that none are typical of the disease and the patient may be referred to any specialist clinic that you can mention. In fact, today in the United Kingdom the commonest presentation is the patient with no definite symptoms who is found by chance to have a raised serum calcium level. Laboratory tests A firm diagnosis cannot be made on clinical features alone. Diagnosis is made either because clinical suspicion leads to a serum calcium estimation or because of the chance finding of a raised serum calcium level. In the category of clinical suspicion are patients with renal stones or renal colic, those with osteoporosis, and, to a lesser extent, patients with a peptic ulcer or with acute pancreatitis. All such patients should be screened for hyper4) MISCELLANEOUS GROUP Peptic ulceration sometimes occurs; it is prob- parathyroidism. ably due to stimulation of gastrin-secreting cells by the hypercalcaemia. Acute pancreatitis is another unusual presentation. Only rarely is a parathyroid tumour large enough to be palpated clinically. Rare too is the incidence of the multiple endocrine neoplasia (MEN) syndrome which is often associated with a parathyroid tumour or parathyroid hyperplasia. A rare but very interesting presentation is neonatal tetany in a baby born to a mother with unsuspected hyperparathyroidism. Because the mother has hypercalcaemia and the calcium crosses the placenta the serum calcium concentration of the developing fetus is also raised so that the fetal parathyroid glands are suppressed. Soon after birth the baby becomes hypocalcaemic and it is some days before its suppressed parathyroid glands recover. Parathyroid crisis is due to a marked hypercalcaemia-usually with a serum calcium level approaching 4 mmol/l (I6 mg/Ioo ml). Nausea and vomiting are the principal symptoms and the resulting dehydration increases the FIG. 2 Gross spinal deformity in a 70-year-old serum calcium level to such an extent that woman with a large parathyroid adenoma.
364
James S Hilary Wade DIAGNOSIS CERTAIN
activity-as occurs, for example, in thyrotoxicosis. It is important to appreciate that if * Hypercalcaemia a patient has hypercalcemia due to any cause other than hyperparathyroidism PTH cannot + Raised P T H i. e. > 1. 0 ng/ml. be detected in the serum. The reason for this is the feedback mechanism between paraOR thyroid activity and the serum calcium level: * Hypercalcaemia parathyroid secretion is suppressed by a raised + Normal (but detectable) P T H serum calcium level unless one or more of the i.e.
