DISEASES OF MANY GLANDS
Multiple gland failure
This is caused by autoimmune disease as detailed. Commonest are the associations of primary hypothyroidism and type 1 diabetes, and either of these with Addison’s disease or pernicious anaemia.
Multiple endocrine neoplasia
This is the name given to the simultaneous or metachronous recurrence of tumours involving a number of endocrine glands. They are inherited in an autosomal dominant manner and are thought to arise from the expression of a recessive oncogenic mutation, which has now been isolated.
Affected persons may pass on the mutation to their offspring in the germ cell, but for the disease to become evident a somatic mutation must also occur, e.g. deletion or loss of a normal homologous chromosome. The defect in MEN 1 is on the long arm of chromosome 11 near an area containing a number of oncogenes that encode for proteins with fibroblastic growth factor activity. The gene for MEN 2a is on chromosome 10 close to the retinol binding gene.
Screening unaffected members of a family shows that a significant number of affected individuals are unrecognized, especially with hypercalcaemia.
Treatment is surgical.
TYPE 1. All four parathyroid glands are removed (as all may be involved) followed by vitamin D (1,25- dihydrocalciferol) replacement therapy. Pancreatic tumours are often multiple and recurrence after partial pancreatectomy is invariable. Other tumours are treated surgically if necessary.
TYPE 2. Tumours may also be recurrent or bilateral and a careful follow-up is necessary.
Anxiety or panic attacks
Nausea and/or vomiting
Constipation or diarrhoea
Hypertension-intermittent or constant
Tachycardia plus arrhythmias
Pallor or flushing
(Signs of hypertensive damage)
A careful family history should first be taken. If negative, it does not exclude involvement and it may need repeating at regular (1-5 year) intervals.
1 Type 1. Fasting calcium estimation (if elevated, look for other manifestations of MEN 1). 2 Type 2
(a) Medullary carcinoma of thyroid (MCT). Pentagastrin and calcium infusion test with measurement of calcitonin to pick up ‘C’ cell hyperplasia: doubling of the calcitonin level is abnormal.
(b) Phaeochromocytoma. VMA and metanephrine estimations.
ECTOPIC HORMONE SECRETION
This terminology refers to hormone synthesis, and normally secretion, from a neoplastic non-endocrine cell, most usually seen in tumours that have some degree of embryological resemblance to specialist endocrine cells. Multiple theories have been advanced to explain the occurrence. The clinical effects may be those of the hor- .mone produced, with or without manifestations of systemic malignancy.
The commonest situations seen are:
HYPERCALCAEMIA OF MALIGNANT DISEASE, often from squamous cell tumours of lung and breast, often with bone metastases. It is mediated by many different factors, but very rarely by PTH itself; a PTH-related protein (PTHrP) with considerable sequence homology has recently been isolated and appears to be the most frequent cause.
SIAD H. Again, this is commonest from a primary lung tumour. ECTOPIC ACTH SYNDROME. Small-cell carcinoma of the lung, carcinoid tumours and medullary thyroid carcinomas are the commonest causes.
PRODUCTION OF INSULIN-LIKE ACTIVITY may result in hypoglycaemia.
ENDOCRINE TREATMENT OF OTHER MALIGNANCIES
Endocrine forms of treatment for malignancy have been used for many years, for example oophorectomy for breast cancer and orchidectomy for prostatic malignancy. Newer more acceptable therapies include the antioestrogen tamoxifen for breast carcinoma and the LHRH analogues, buserelin and goserelin, for prostatic cancer.